Cyclopropyl-amide compounds as dual LSD1/HDAC inhibitors

ABSTRACT

The present disclosure describes novel compounds of the general Formula (I), their analogs, tautomeric forms, stereoisomers, polymorphs, hydrates, solvates, pharmaceutically acceptable salts, pharmaceutical compositions, metabolites, and prodrugs thereof. These compounds can inhibit both LSD and HDAC and are useful as therpeautic or ameliorating agent for diseases that are involved in cellular growth such as malignant tumors, schizophrenia, Alzheimer&#39;s disease, parkinson&#39;s disease and the like.

TECHNICAL FIELD

Described are novel derivatives of the Formula (I), their analogs,tautomeric forms, stereoisomers, geometrical isomers, polymorphs,hydrates, solvates, pharmaceutically acceptable salts, pharmaceuticalcompositions, metabolites, and prodrugs thereof.

Also, described herein is the process for the preparation of the abovesaid novel derivatives of the Formula (I), their analogs, stereoisomers,diastereomers, polymorphs, hydrates, solvates, pharmaceuticallyacceptable salts, pharmaceutical compositions, metabolites, prodrugs,and intermediates useful in the preparation of such compounds.

The compounds described herein are dual inhibitors of lysine specificdemethylase (LSD) and histone deacetylase (HDAC) and also arrest cellgrowth in neoplastic cells, thereby inhibiting proliferation. Thesecompounds can be used as prophylactic or therapeutic agents for treatingcancer, schizophrenia, Alzheimer's disease, Parkinson's disease, and thelike.

BACKGROUND

Transcriptional regulation is a major event in cell differentiation,proliferation and apoptosis. Transcriptional activation of a set ofgenes determines cellular function and is tightly regulated by a varietyof factors. One of the regulatory mechanisms involved in this process isan alteration in the tertiary structure of DNA, which affectstranscription factors to their target DNA regiments. Nucleosomalintegrity is regulated by the acetylation status of the core histone,with the result being permissiveness to transcription. The regulationsof transcription factor are thought to involve changes in the structureof chromatin. Changing the affinity of histone proteins for coiled DNAin the nucleosome alters the structure of chromatin. Hypoacetylatedhistones are believed to have greater affinity to the DNA and form atightly bound DNA-histone complex and render the DNA inaccessible totranscriptional regulation. The acetylating status of the histone isgoverned by the balanced activities of the histone acetyl transferase(HAT) and histone deacetylase (HDAC).

Human histone deacetylases (HDACs) are classified into two distinctclasses, the HDACs and sirtuins. The HDACs are divided into twosubclasses based on their similarity to yeast histone deacetylases, RPD3 (class I includes HDAC 1, 2, 3, and 8) and Hda 1 (class II includesHDAC 4, 6, 7, 9, and 10). All the HDACs have a highly conserved zincdependent catalytic domain. There is growing evidence that theacetylation state of proteins and thus the HDAC enzyme family plays acrucial role in the modulation of several biological processes,including transcription and cell cycle. Several structural classes ofHDAC inhibitors have been identified and are reviewed in Marks et al.,J. Natl. Cancer Inst., 2000, 92, 1210-1215; L. Zhang, et. al., MedicinalResearch Reviews, 2015, 35, 63-84; P. K. Agrawala, et. al., HOAJ Biology2013, 2, 1-8. Other compounds that are able to inhibit HDAC activity areTrichostatin A (TSA), PXDlOl, Tropoxin (TPX), Sodium butyrate (NaB),Sodium valproate (VPA), Cyclic hydroxamic acid containing peptides(CHAPs), Depsipeptide FK-228, MGCDO103 and MS-275. The above mentionedinhibitors can also de-repress tumor suppressor genes (e.g. p21wafl/cf1), resulting in antiproliferative effects in vitro and anti tumoreffects in vivo. At present, there are four HDAC inhibitors that havebeen approved by FDA for the treatment of various cancers. Vorinostat,Isotdax and Belinostat have been approved for the treatment of CutaneousT-Cell Lymphoma and panibinostat has been approved for the treatment ofmultiple myeloma.

Another group of enzymes known as lysine methyl transferases and lysinedemethylases are involved in the modulation of histone methylation.Lysine demethylases (LSD1 and LSD2) are known to remove methyl groupfrom mono and dimethylated Lys4 of histone H3 (H3K4me1/2) through flavinadenine dinucleotide (FAD) dependent enzymatic oxidation and releasingformaldehyde as the byproduct. LSD1 mediated demethylation is notrestricted to histones; other non-histone substrates such as p53, STAT3,E2F1, and MYPT1 are also demethylated leading to a change in cellularfunctions. LSD1 is overexpressed in various cancer cells and tissues,neuroblastoma, prostate cancer, breast cancer, leukemia, lung cancer andbladder cancer cells. It is known that either inhibition of LSD1 withsmall molecule or by RNAi is associated with inhibition of cancer cellgrowth by modulating prosurvival gene expression and p53 transcriptionalactivity. Several novel irreversible inhibitors of LSD1 have beendescribed in literature and two compounds ORY-1001 and GSK-2879552 haveentered phase 1 clinical trial, (N. Miyata, et. al., J. Med. Chem, 54,8236-8250, 2011; R. P. Clausen, et. al., Bioorg. Med. Chem., 19,3625-3636, 2011; J. W. Hφfeldt, et. al., Nature Drug Discovery, 12,917-930, 2013, Manfred Jung and et. al., Clinical Epigenetics (2016)8:57).

Another recent report suggests that a cross talk between LSD1 and HDACis associated with changes in gene expression that leads to growthinhibition and apoptosis (Huang et. al. Carcinogenesis, 34, 1196-1207,2013). This and other similar studies suggest that the inhibition ofboth LSD1 and HDAC can exhibit synergyism in modulating gene expressionand in inducing growth inhibition. Singh, et al., (Neuro-Oncology, 13,894-903, 2011) have demonstrated that combined inhibition of LSD1 andHDAC can lead to cooperative regulation of key pathways of cell death inglioblastoma multiforme (GBM, a form of aggressive brain tumor). Fiskus,et al., (Leukemia, 1-10, 2014) have shown that combined treatment ofLSD1 inhibitor SP2509 and HDAC inhibitor panobinostat wassynergistically lethal against cultured and primary AML blasts. In miceengrafted with human AML cells, combined treatment of both SP2509 andpanobinostat significantly improved the survival compared with eitherSP2509 or Panobinostat.

Cole, et al., have disclosed LSD1/HDAC dual inhibitors and their utilityin treating various disease conditions or disorders (US2017/0029366).

Although, there are several chemotherapies and target therapies baseddrugs for cancer, an effective cure for cancer still remains elusive.Further, development of acquired resistance and disease relapse aremajor issues that still need to be addressed. Therefore, there is a needfor novel mechanism-based approaches in the treatment of cancer, thatwould have a stronger effect on a signaling pathway and/or affectmultiple pathways and mutually exclusive mechanisms in the cells. Inthis regard, novel dual inhibitors of LSD-1/HDAC will have betterefficacy in treating multiple cancers compared to either treating withLSD-1 or HDAC inhibitors alone.

Objective

One objective herein is to provide a compound of Formula (I) theiranalogs, tautomeric forms, stereoisomers, polymorphs, solvates,intermediates, pharmaceutically acceptable salts, metabolites, andprodrugs thereof.

Another objective herein is to provide a pharmaceutical composition withthe novel derivatives of the Formula (I).

Yet another objective herein is to provide a method of preventing ortreating proliferative diseases by administering a therapeutic amount ofnovel compound of the Formula (I) or a pharmaceutically acceptable saltand/or prodrug.

SUMMARY

The present disclosure describes compound of Formula I

their analogs, tautomeric forms, stereoisomers, polymorphs, solvates,intermediates, pharmaceutically acceptable salts, metabolites, andprodrugs thereof, whereinAr is selected from the group consisting of substituted or unsubstitutedC₅₋₆aryl, C₁₋₆ heteroaryl, and C₂₋₁₀ heterocyclyl with heteroatomsselected from N, O, S;W represents a bond or CR₄R₅, whereinR₄ and R₅ are independently selected from the group consisting ofhydrogen, substituted or unsubstituted C₁₋₈ alkyl, C₅₋₆ aryl, and C₁₋₆heteroaryl with heteroatoms selected from N, O, S;Y is a bond or is selected from the group consisting of substituted orunsubstituted C₁₋₈ alkyl, C₁₋₈ alkenyl, C₁₋₈ alkynyl, C₅₋₆ aryl, C₁₋₆heteroaryl, C₂₋₁₀ heterocyclyl, C₃₋₈ cycloalkyl, —CO—, and —CO—C₂₋₁₀heterocyclyl;wherein C₁₋₈ alkyl, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₂₋₁₀ heterocyclyl, C₃₋₈cycloalkyl, is optionally substituted with one or more of the groupsselected from hydrogen, C₁₋₆ alkyl, oxo (═O), C₃₋₈ cycloalkyl, halogen,OH, and cyano;Z represents a bond or is selected from the group consisting of C₁₋₈alkyl, C₁₋₈ alkenyl, C₁₋₈ alkynyl, C₇₋₁₂-alkylaryl, C₇₋₁₂-alkenylaryl,C₇₋₁₅-arylalkenyl, C₂₋₁₂-alkylheteroaryl, —CO—C₇₋₁₂ alkylaryl, —CO—C₇₋₁₂alkenylaryl, —CONR₆—C₁₋₈ alkyl, —NR₆CO—C₁₋₈ alkyl-, —NR₆—C₁₋₈ alkyl,—O—C₁₋₈ alkyl-, —CONR₆—C₅₋₆ aryl-, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₂₋₁₀heterocyclyl, —CO—C₂₋₁₀ heterocyclyl, —NR₆—CO—OC₁₋₈ alkyl, O—CO—NR₆—C₁₋₈alkyl, —NR₆CO—C₅₋₆ aryl-, —NR₆—C₅₋₆ aryl, —NR₆—C₁₋₆ heteroaryl, —C₁₋₈alkyl-O—C₅₋₆ aryl, —O—C₅₋₆ aryl, O—C₁₋₆ heteroaryl, —NR₆—CO—OC₅₋₆ aryl,—CONR₆—C₇₋₁₂ alkylaryl, —CONR₆—C₇₋₁₂ alkenylaryl, —SO₂—C₅₋₆ aryl,—SO₂—C₇₋₁₂ alkylaryl, —NR₆SO₂—C₇₋₁₂ alkylaryl, C₁₋₈ alkyl-CONR₆—C₅₋₆aryl, and O—CO—NR₆—C₅₋₆ aryl;R₆ is selected from the group consisting of hydrogen, C₁₋₈ alkyl, C₁₋₆haloalkyl, C₃₋₈ cycloalkyl, C₅₋₆ aryl, and C₁₋₆ heteroaryl, withheteroatoms selected from N, O, S;R₁ is selected from the group consisting of hydrogen, halogen, hydroxy,nitro, cyano, azido, nitroso, oxo (═O), thioxo (═S), —SO₂—, amino,hydrazino, formyl, C₁₋₈ alkyl, C₁₋₈ haloalkyl, C₁₋₈ alkoxy, C₁₋₈haloalkoxy, C₇₋₁₂ arylalkoxy, C₃₋₈ cycloalkyl, C₃₋₈ cycloalkyloxy, C₅₋₆aryl, C₂₋₁₀ heterocyclyl, C₁₋₆ heteroaryl, alkylamino, —COOR_(a),—C(O)R_(b), —C(S)R_(a), —C(O)NR_(a)R_(b), —C(S)NR_(a)R_(b),—NR_(a)C(O)NR_(b)R_(c), NR_(a)C(S)NR_(b)R_(c), —N(R_(a))SOR_(b),—N(R_(a))SO₂R_(b), —NR_(a)C(O)OR_(b), —NR_(a)R_(b), —NR_(a)C(O)R_(b)—,—NR_(a)C(S)R_(b)—, —SONR_(a)R_(b)—, —SO₂NR_(a)R_(b)—, —OR_(a),—OR_(a)C(O)OR_(b)—, —OC(O)NR_(a)R_(b), OC(O)R_(a), —OC(O)NR_(a)R_(b)—,—R_(a)NR_(b)R_(c), —R_(a)OR_(b)—, —SR_(a), —SOR_(a) and —SO₂R_(a),wherein R_(a), R_(b) and R_(c) is independently selected from the groupconsisting of hydrogen, C₁₋₈ alkyl, C₃₋₈ cycloalkyl, C₅₋₆ aryl, C₇₋₁₅arylalkyl, C₂₋₁₀ heterocyclyl, C₁₋₆ heteroaryl, and C₂₋₁₂heteroarylalkyl with heteroatoms selected from N, O, S;wherein C₇₋₁₂ arylalkoxy, C₁₋₈ alkyl, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₂₋₁₀heterocyclyl, C₃₋₈ cycloalkyl, is optionally substituted with one ormore of the groups selected from hydrogen, C₁₋₆ alkyl, C₅₋₆ aryl, C₁₋₆heteroaryl, C₂₋₁₀ heterocyclyl, oxo (═O), C₃₋₈ cycloalkyl, halogen, OH,amino, and cyano;R₃ is selected from the group consisting of hydrogen, substituted orunsubstituted C₁₋₈ alkyl, and C₅₋₆ aryl;R₂ is selected from the group consisting of —OR₇, aniline, amino C₅₋₆aryl, and amino C₁₋₆ heteroaryl,wherein aniline, amino C₅₋₆ aryl, and amino C₁₋₆ heteroaryl, isoptionally substituted with one or more of the groups selected from C₁₋₈alkyl, halogen, OH, amino, and cyano; R₇ is selected from the groupconsisting of hydrogen, C₁₋₈ alkyl, C₅₋₆ aryl, C₂₋₁₀ heterocyclyl and—COR₈, wherein R₈ is selected from the group consisting of C₁₋₈ alkyl,C₅₋₆ aryl, C₁₋₆ heteroaryl, C₃₋₈ cycloalkyl, and C₂₋₁₀ heterocyclyl.

These and other features, aspects, and advantages of the present subjectmatter will become better understood with reference to the followingdescription. This summary is provided to introduce a selection ofconcepts in a simplified form. This summary is not intended to identifykey features or essential features of the disclosure, nor is it intendedto be used to limit the scope of the subject matter.

BRIEF DESCRIPTION OF THE ACCOMPANYING DRAWINGS

The following drawings form part of the present specification and areincluded to further illustrate aspects of the present disclosure. Thedisclosure may be better understood by reference to the drawings incombination with the detailed description of the specific embodimentspresented herein.

FIG. 1 depicts the modulation of Tubulin and Histone Acetylation inMM.1S cells, in accordance with an embodiment of the present disclosure.

FIG. 2 depicts the efficacy study in multiple myeloma model, inaccordance with an embodiment of the present disclosure.

FIG. 3 depicts the modulation of CD86 and CD11b in MV411 cells, inaccordance with an embodiment of the present disclosure.

DETAILED DESCRIPTION

Those skilled in the art will be aware that the present disclosure issubject to variations and modifications other than those specificallydescribed. It is to be understood that the present disclosure includesall such variations and modifications. The disclosure also includes allsuch steps, features, compositions and compounds referred to orindicated in this specification, individually or collectively, and anyand all combinations of any or more of such steps or features.

Definitions

For convenience, before further description of the present disclosure,certain terms employed in the specification, and examples are collectedhere. These definitions should be read in the light of the remainder ofthe disclosure and understood as by a person of skill in the art. Theterms used herein have the meanings recognized and known to those ofskill in the art, however, for convenience and completeness, particularterms and their meanings are set forth below.

The articles “a”, “an” and “the” are used to refer to one or to morethan one (i.e., to at least one) of the grammatical object of thearticle.

The terms “comprise” and “comprising” are used in the inclusive, opensense, meaning that additional elements may be included. Throughout thisspecification, unless the context requires otherwise the word“comprise”, and variations, such as “comprises” and “comprising”, willbe understood to imply the inclusion of a stated element or step orgroup of element or steps but not the exclusion of any other element orstep or group of element or steps.

The term “including” is used to mean “including but not limited to”.“Including” and “including but not limited to” are used interchangeably.

In the structural formulae given herein and throughout the presentdisclosure, the following terms have been indicated meaning, unlessspecifically stated otherwise.

Furthermore, the compound of Formula (I) can be its derivatives,analogs, tautomeric forms, stereoisomer's, diastereomers, geometricalisomers, polymorphs, solvates, intermediates, metabolites, prodrugs orpharmaceutically acceptable salts and compositions.

The compounds described herein may contain one or more chiral centersand/or double bonds and therefore, may exist as stereoisomers, such asdouble-bond isomers (i.e., geometric isomers), regioisomers, enantiomersor diastereomers. Accordingly, the chemical structures depicted hereinencompass all possible enantiomers and stereoisomers of the illustratedor identified compounds including the stereoisomerically pure form(e.g., geometrically pure, enantiomerically pure or diastereomericallypure) and enantiomeric and stereoisomeric mixtures. Enantiomeric andstereoisomeric mixtures can be resolved into their component enantiomersor stereoisomers using separation techniques or chiral synthesistechniques well known to the person skilled in the art. The compoundsmay also exist in several tautomeric forms including the enol form, theketo form and mixtures thereof. Accordingly, the chemical structuresdepicted herein encompass all possible tautomeric forms of theillustrated or identified compounds. It is also understood that someisomeric form such as diastereomers, enantiomers and geometrical isomerscan be separated by physical and/or chemical methods and by thoseskilled in the art. Pharmaceutically acceptable solvates may be hydratesor comprising of other solvents of crystallization such as alcohols,ether, and the like.

The term “solvate”, as used herein, refers to a crystal lattice whichcontains solvent.

The term “hydrate” refers to a more specific form of solvate, whereinthe solvent is water.

As used herein, the term “substituted” is contemplated to include allpermissible substituents of organic compounds. In a broad aspect, thepermissible substituents include acyclic and cyclic, branched andunbranched, carbocyclic and heterocyclic, aromatic and nonaromaticsubstituents of organic compounds. Illustrative substituents, forexample, include those described herein above. The permissiblesubstituents can be one or more and the same or different forappropriate organic compounds. For purposes of this disclosure, theheteroatoms such as nitrogen may have hydrogen substituents and/or anypermissible substituents of organic compounds described herein whichsatisfy the valences of the heteroatoms.

The term “polymorphs” refers to crystal forms of the same molecule, anddifferent polymorphs may have different physical properties such as, forexample, melting temperatures, heats of fusion, solubilities,dissolution rates and/or vibrational spectra as a result of thearrangement or conformation of the molecules in the crystal lattice.

The term “prodrugs” refers to the precursor of the compound of Formula(I), which on administration undergoes chemical conversion by metabolicprocesses before becoming active pharmacological substances. In general,such prodrugs will be functional derivatives of a compound of theinvention, which are readily convertible in vivo into a compound of theinvention.

The term “alkyl” refers to straight or branched aliphatic hydrocarbongroups having the specified number of carbon atoms, which are attachedto the rest of the molecule by a single atom, which may be optionallysubstituted by one or more substituents. Preferred alkyl groups include,without limitation, methyl, ethyl, n-propyl, isopropyl, butyl, isobutyl,t-butyl, pentyl, hexyl, heptyl, octyl and the like.

The term “aryl” refers to aromatic radicals having 6 to 14 carbon atoms,which may be optionally substituted by one or more substituents.Preferred aryl groups include, without limitation, phenyl, naphthyl,indanyl, biphenyl, and the like.

The term “arylalkyl” refers to an aryl group directly bonded to an alkylgroup, which may be optionally substituted by one or more substituents.Preferred arylalkyl groups include, without limitation, —CH₂C₆H₅,—C₂H₄C₆H₅, and the like.

The term “heterocyclyl” refers to a heterocyclic ring radical which maybe optionally substituted by one or more substituents. The heterocyclylring radical may be attached to the main structure at any heteroatom orcarbon atom that results in the creation of a stable structure.

Furthermore, the term “heterocyclyl” refers to a stable 3 to 15 memberedrings radical, which consists of carbon atoms and from one to fiveheteroatoms selected from nitrogen, phosphorus, oxygen and sulfur. Forpurposes of this invention the heterocyclic ring radical may bemonocyclic, bicyclic or tricyclic ring systems, and the nitrogen,phosphorus, carbon, or sulfur atoms in the heterocyclic ring radical maybe optionally oxidized to various oxidation states. In addition, thenitrogen atom may be optionally quaternized; and the ring radical may bepartially or fully saturated. Preferred heterocyclyl groups include,without limitation, azetidinyl, acridinyl, benzodioxolyl, benzodioxanyl,benzofuranyl, carbazolyl, cinnolinyl, dioxolanyl, indolizinyl,naphthyridinyl, perhydroazepinyl, phenazinyl, phenothiazinyl,phenoxazinyl, phthalazinyl, pyridyl, pteridinyl, purinyl, quinazolinyl,qunioxalinyl, quinolinyl, isoquinolinyl, tetrazolyl, imidazolyl,tetrahydroisoquinolinyl, piperidinyl, piperazinyl, homopiperazinyl,2-oxoazepinyl, azepinyl, pyrrolyl, 4-piperidonyl, pyrrolidinyl,pyrazinyl, pyrimidinyl, pyridazinyl, oxazolyl, oxazolinyl, triazolyl,indanyl, isoxazolyl, isoxazolidinyl, thiazolyl, thiazolinyl,thiazolidinyl, isothiazolyl, quinuclidinyl, isothiazolidinyl, indolyl,isoindolyl, indolinyl, isoindolinyl, octahydroindolyl,octahydroisoindolyl, quinolyl, isoquinolyl, decahydroisoquinolyl,benzimidazolyl, thiadiazolyl, benzopyranyl, benzothiazolyl,benzooxazolyl, thienyl, morpholinyl, thiomorpholinyl, thiamorpholinylsulfoxide, furyl, tetrahydrofuryl, tetrahydropyranyl, chromanyl, andisochromanyl.

The term “heteroaryl” refers to an aromatic heterocyclic ring radical asdefined above. The heteroaryl ring radical may be attached to the mainstructure at any heteroatom or carbon atom that results in the creationof stable structure.

The term “heteroarylalkyl” refers to a heteroaryl group directly bondedto an alkyl group, which may be optionally substituted by one or moresubstituents. Preferred heteroarylalkyl groups include, withoutlimitation, —CH₂-pyridinyl, —C₂H₄-furyl and the like.

The term “fused heterocyclyl” refers to monocyclic or polycyclic ring,polycyclic ring system refers to a ring system containing 2 or morerings, preferably bicyclic or tricyclic rings, in which rings can befused, bridged or spiro rings or any combinations thereof. A fused ringas used herein means that the two rings are linked to each other throughtwo adjacent ring atoms common to both rings. The fused ring can contain1-4 hetero atoms independently selected from N, O, and S. The rings canbe either fused by nitrogen or —CH— group.

The term“bridged ring” as used herein means that a ring comprises alinker group (C(Rq)₂)p-linking together any two non-adjacent carbon ornitrogen atoms of the ring, where p is 1 or 2 and each independently ishydrogen or C₁₋₄ alkyl.

The term “cycloalkyl” refers to non-aromatic mono or polycyclic ringsystem of about 3 to 12 carbon atoms, which may be optionallysubstituted by one or more substituents. The polycyclic ring denoteshydrocarbon systems containing two or more ring systems with one or morering carbon atoms in common i.e. a spiro, fused or bridged structures.Preferred cycloalkyl groups include, without limitation, cyclopropyl,cyclobutyl, cyclopentyl, cyclohexyl, cyclooctanyl, perhydronaphthyl,adamantyl, noradamantyl and norbornyl groups, bridged cyclic groups orspirobicyclic groups e.g spiro [4.4] non-2-yl and the like.

The term “alkoxy” refers to an alkyl group attached via an oxygenlinkage to the rest of the molecule, which may be optionally substitutedby one or more substituents. Preferred alkoxy groups include, withoutlimitation, —OCH₃, —OC₂H₅ and the like.

The term “alkylthio” refers to an alkyl group attached via a sulfurlinkage to the rest of the molecule, which may be optionally substitutedby one or more substituents. Preferred alkylthio groups include, withoutlimitation, —SCH₃, —SC₂H₅ and the like.

The term “alkylamino” refers to an alkyl group as defined above attachedvia amino linkage to the rest of the molecule, which may be optionallysubstituted by one or more substituents. Preferred alkylamino groupsinclude, without limitation —NHCH₃, —N(CH₃)₂, and the like.

The term “alkenyl” refers to an aliphatic hydrocarbon group containing acarbon-carbon double bond and which may be straight or branched chainhaving about 2 to 10 carbon atoms, which may be optionally substitutedby one or more substituents. Preferred alkenyl groups include, withoutlimitation, ethenyl, 1-propenyl, 2-propenyl, iso-propenyl,2-methyl-1-propenyl, 1-butenyl, 2-butenyl and the like.

The term “alkynyl” refers to a straight or branched hydrocarbyl radicalshaving at least one carbon-carbon triple bond and having in the range of2-12 carbon atoms, which may be optionally substituted by one or moresubstituents. Preferred alkynyl groups include, without limitation,ethynyl, propynyl, butynyl and the like.

The term “alkylaryl” refers to an alkyl group directly bonded to an arylgroup, which may be optionally substituted by one or more substituents.Preferred alkylaryl groups include, without limitation, —CH₂-phenyl,—C₂H₄-phenyl, C₃H₆-phenyl and the like.

The term “alkenylaryl” refers to an alkenyl group directly bonded to anaryl group, which may be optionally substituted by one or moresubstituents. Preferred alkenylaryl groups include, without limitation,—CH═CH-phenyl, —CH₂—CH═CH— phenyl and the like.

The term “arylalkenyl” refers to an aryl group directly bonded to analkenyl group, which may be optionally substituted by one or moresubstituents. Preferred arylalkenyl groups include, without limitation,—C₆H₅—CH═CH—, —C₆H₅—CH═CH—CH₂ and the like.

The term “arylalkynyl” refers to an aryl group directly bonded to analkynyl group, which may be optionally substituted by one or moresubstituents. Preferred arylalkenyl groups include, without limitation,—C₆H₅-ethynyl, —C₆H₅-propynyl, and the like

The term “—CO-alkylaryl” refers to a carbonyl group directly attached toan alkylaryl group which may be optionally substituted by one or moresubstituents. Preferred “—CO-alkylaryl” groups include, withoutlimitations, —CO—CH₂-phenyl, —CO—C₂H₄-phenyl and the like

The term “—CO-alkenylaryl” refers to a carbonyl group directly attachedto an alkenylaryl group which may be optionally substituted by one ormore substituents. Preferred “—CO-alkenylaryl” groups include, withoutlimitations, —CO—CH═CH-phenyl, —CO—CH₂—CH═CH-phenyl and the like.

The term “—CO-heterocyclyl” refers to a carbonyl group directly attachedthrough the heteratom or carbon atom of a heterocyclyl group which maybe optionally substituted by one or more substitutents. Preferred“—CO-heterocyclyl” groups include, without limitations, —CO-piperazinyl,—CO—N-piperdinyl (implies attachment is through the nitrogen ofpiperdinyl group), —CO—C-piperidinyl (implies the attachment is throughthe carbon of piperdinyl group) and the like

The term “alkyl-O-aryl-” refers to an alkyl group attached to arylthrough the oxygen linker which may be optionally substituted by one ormore substitutents. Preferred groups without limitationsinclude-(CH₂)₂—O-phenyl- and the like.

The term-“—SO₂alkylaryl-” refers to a —SO₂— group attached to alkylarylgroup which may be optionally substituted by one or substitutents.Preferred ‘—SO₂alkylaryl-’ groups include —SO₂—CH₂-Aryl and the like.

It is understood that included in the family of compounds of Formula (I)are isomeric forms including diastereoisomers, enantiomers, tautomers,and geometrical isomers in “E” or “Z” configurational isomer or amixture of ‘E’ and ‘Z’ isomers. It is also understood that some isomericform such as diastereomers, enantiomers and geometrical isomers can beseparated by physical and/or chemical methods and by those skilled inthe art.

Compounds disclosed herein may exist as single stereoisomers, racematesand or mixtures of enantiomers and/or diastereomers. All such singlestereoisomers, racemates and mixtures thereof are intended to be withinthe scope of the subject matter described.

Compounds disclosed herein include isotopes of hydrogen, carbon, oxygen,fluorine, chlorine, iodine and sulfur which can be incorporated into thecompounds, such as not limited to ²H (D), ³H (T), c ¹¹C, ¹³C, ¹⁴C, ¹⁵N,¹⁸F, ³⁵S, ³⁶Cl and ¹²⁵I. Compounds of this invention where in atoms wereisotopically labeled for example radioisotopes such as ³H, ¹³C, ¹⁴C, andthe like can be used in metabolic studies, kinetic studies and imagingtechniques such as positron emission tomography used in understandingthe tissue distribution of the drugs. Compounds of the invention wherehydrogen is replaced with deuterium may improve the metabolic stabilityand pharmacokinetics properties of the drug such as in vivo half life.Compounds of the invention where isotopically labeled ¹⁸F can be usefulas PET imaging studies.

The phrase “pharmaceutically acceptable” refers to compounds orcompositions that are physiologically tolerable and do not typicallyproduce allergic or similar untoward reaction, including but not limitedto gastric upset or dizziness when administered to subjects.

Pharmaceutically acceptable salts forming part of this invention includesalts derived from inorganic bases such as like Li, Na, K, Ca, Mg, Fe,Cu, Zn and Mn and ammonium, substituted ammonium salts, aluminum saltsand the like; salts of organic bases such as N,N′-diacetylethylenediamine, glucamine, triethylamine, choline,dicyclohexylamine, benzylamine, trialkylamine, thiamine, guanidine,diethanolamine, α-phenylethylamine, piperidine, morpholine, pyridine,hydroxyethylpyrrolidine, hydroxyethylpiperidine and the like, salts alsoinclude amino acid salts such as glycine, alanine, cystine, cysteine,lysine, arginine, phenylalanine, guanidine etc. Salts may include acidaddition salts where appropriate which are sulphates, nitrates,phosphates, perchlorates, borates, hydrohalides, acetates, tartrates,maleates, fumarates, citrates, succinates, palmoates,methanesulphonates, tosylates, benzoates, salicylates,hydroxynaphthoates, benzenesulfonates, ascorbates, glycerophosphates,ketoglutarates and the like.

Described herein are prodrugs of the compound of Formula (I), which onadministration undergo chemical conversion by metabolic processes beforebecoming active pharmacological substances. In general, such prodrugswill be functional derivatives of a compound of the invention, which arereadily convertible in vivo into a compound of the invention.

The compounds described herein can also be prepared in any solid orliquid physical form, for example the compound can be in a crystallineform, in amorphous form and have any particle size. Furthermore, thecompound particles may be micronized or nanoized, or may beagglomerated, particulate granules, powders, oils, oily suspensions orany other form of solid or liquid physical forms.

The compounds described herein may also exhibit polymorphism. Thisinvention further includes different polymorphs of the compounds of thepresent invention. The term polymorph refers to a particular crystallinestate of a substance, having particular physical properties such asX-ray diffraction, IR spectra, melting point and the like.

The terms “histone deacetylase” and “HDAC” are intended to refer to anyone of a family of enzymes that remove acetyl groups from the ε-aminogroups of lysine residues at the N-terminus of a histone or tubulin.Unless otherwise indicated by context, the term “histone” is meant torefer to any histone protein, including H1, H2A, H2B, H3, H4 and H5,from any species. Human HDAC proteins or gene products include but arenot limited to, HDAC-1, HDAC-2, HDAC-3, HDAC-4, HDAC-5, HDAC-6, HDAC-7,HDAC-8, HDAC-9, HDAC-10 and HDAC-11. The histone deacetylase can also bederived from a protozoal or fungal source.

The term “histone deacetylase inhibitor” or “inhibitor of histonedeacetylase” is used to identify a compound, which is capable ofinteracting with a histone deacetylase and inhibiting its activity, moreparticularly its enzymatic activity. Inhibiting histone deacetylaseenzymatic activity means reducing the ability of a histone deacetylaseto remove an acetyl group from a histone or tubulin. Preferably, suchinhibition is specific, i.e. the histone deacetylase inhibitor reducesthe ability of histone deacetylase to remove an acetyl group from ahistone or tubulin at a concentration that is lower than theconcentration of the inhibitor that is required to produce some other,unrelated biological effect.

The term “lysine demethylase inhibitor” or “inhibitor of lysinedemethylase” is used to identify a compound, which is capable ofinteracting with a histone demethylase and inhibiting its activity, moreparticularly its enzymatic activity. Inhibiting histone demethylaseenzymatic activity means reducing the ability of a histone demethylaseto remove a methyl group from a histone. Inhibitor of histonedemethylase involves removal either mono methyl or dimethyl or trimethylgroup from histones. Preferably, such inhibition is specific, i.e. thehistone demethylase inhibitor reduces the ability of histone demethylaseto remove a methyl group from a histone at a concentration that is lowerthan the concentration of the inhibitor that is required to produce someother, unrelated biological effect.

The term ‘Dual inhibitor of LSD-1/HDAC’ is capable of removing acetylgroup from histones or tublin and methyl group from histones. Theseinhibitors are capable of inhibiting more than one HDAC isozyme and allthose isozymes are covered in addition to inhibiting LSD-1 activity

The term dual inhibitor LSD1/HDAC6 is used to identify a compound whichis capable of interacting selectively with HDAC6 enzymes in addition tohaving enzymatic interactions for LSD-1. Dual inhibitor of LSD-1/HDAC6is capable of removing acetyl group from tublin and methyl group fromhistones.

The term dual inhibitor LSD1/HDAC1 is used to identify a compound whichis capable of interacting selectively with HDAC1 enzymes in addition tohaving enzymatic interactions for LSD-1. Dual inhibitor of LSD-1/HDAC 1is capable of removing acetyl group from histones and methyl group fromhistones.

The term dual inhibitor LSD1/HDAC8 is used to identify a compound whichis capable of interacting selectively with HDAC8 enzymes in addition tohaving enzymatic interactions for LSD-1. Dual inhibitor of LSD-1/HDAC8is capable of removing acetyl group from histones and methyl group fromhistones.

A term once described, the same meaning applies for it, throughout thepatent.

In an embodiment of the present invention, there is provided a compoundof Formula I

their analogs, tautomeric forms, stereoisomers, polymorphs, solvates,intermediates, pharmaceutically acceptable salts, metabolites, andprodrugs thereof;whereinAr is selected from the group consisting of substituted or unsubstitutedC₅₋₆aryl, C₁₋₆ heteroaryl, and C₂₋₁₀ heterocyclyl with heteroatomsselected from N, O, S;W represents a bond or CR₄R₅, whereinR₄ and R₅ are independently selected from the group consisting ofhydrogen, substituted or unsubstituted C₁₋₈ alkyl, C₅₋₆ aryl, and C₁₋₆heteroaryl with heteroatoms selected from N, O, S;Y is a bond or is selected from the group consisting of substituted orunsubstituted C₁₋₈ alkyl, C₁₋₈ alkenyl, C₁₋₈ alkynyl, C₅₋₆ aryl, C₁₋₆heteroaryl, C₂₋₁₀ heterocyclyl, C₃₋₈ cycloalkyl, —CO—, and —CO—C₂₋₁₀heterocyclyl;wherein C₁₋₈ alkyl, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₂₋₁₀ heterocyclyl, C₃₋₈cycloalkyl, is optionally substituted with one or more of the groupsselected from hydrogen, C₁₋₆ alkyl, oxo (═O), C₃₋₈ cycloalkyl, halogen,OH, and cyano;Z represents a bond or is selected from the group consisting of C₁₋₈alkyl, C₁₋₈ alkenyl, C₁₋₈ alkynyl, C₇₋₁₂-alkylaryl, C₇₋₁₂-alkenylaryl,C₇₋₁₅-arylalkenyl, C₂₋₁₂-alkylheteroaryl, —CO—C₇₋₁₂ alkylaryl, —CO—C₇₋₁₂alkenylaryl, —CONR₆—C₁₋₈ alkyl, —NR₆CO—C₁₋₈ alkyl-, —NR₆—C₁₋₈ alkyl,—O—C₁₋₈ alkyl-, —CONR₆—C₅₋₆ aryl-, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₂₋₁₀heterocyclyl, —CO—C₂₋₁₀ heterocyclyl, —NR₆—CO—OC₁₋₈ alkyl, O—CO—NR₆—C₁₋₈alkyl, —NR₆CO—C₅₋₆ aryl-, —NR₆—C₅₋₆ aryl, —NR₆—C₁₋₆ heteroaryl, —C₁₋₈alkyl-O—C₅₋₆ aryl, —O—C₅₋₆ aryl, O—C₁₋₆ heteroaryl, —NR₆—CO—OC₅₋₆ aryl,—CONR₆—C₇₋₁₂ alkylaryl, —CONR₆—C₇₋₁₂ alkenylaryl, —SO₂—C₅₋₆ aryl,—SO₂—C₇₋₁₂ alkylaryl, —NR₆SO₂—C₇₋₁₂ alkylaryl, C₁₋₈ alkyl-CONR₆—C₅₋₆aryl, and O—CO—NR₆—C₅₋₆ aryl;R₆ is selected from the group consisting of hydrogen, C₁₋₈ alkyl, C₁₋₆haloalkyl, C₃₋₈ cycloalkyl, C₅₋₆ aryl, and C₁₋₆ heteroaryl, withheteroatoms selected from N, O, S;R₁ is selected from the group consisting of hydrogen, halogen hydroxy,nitro, cyano, azido, nitroso, oxo (═O), thioxo (═S), —SO₂—, amino,hydrazino, formyl, C₁₋₈ alkyl, C₁₋₈ haloalkyl, C₁₋₈ alkoxy, C₁₋₈haloalkoxy, C₇₋₁₂ arylalkoxy, C₃₋₈ cycloalkyl, C₃₋₈ cycloalkyloxy, C₅₋₆aryl, C₂₋₁₀ heterocyclyl, C₁₋₆ heteroaryl, alkylamino, —COOR_(a),—C(O)R_(b), —C(S)R_(a), —C(O)NR_(a)R_(b), —C(S)NR_(a)R_(b),—NR_(a)C(O)NR_(b)R_(c), NR_(a)C(S)NR_(b)R_(c), —N(R_(a))SOR_(b),—N(R_(a))SO₂R_(b), —NR_(a)C(O)OR_(b), —NR_(a)R_(b), —NR_(a)C(O)R_(b)—,—NR_(a)C(S)R_(b)—, —SONR_(a)R_(b)—, —SO₂NR_(a)R_(b)—, —OR_(a),—OR_(a)C(O)OR_(b)—, —OC(O)NR_(a)R_(b), OC(O)R_(a), —OC(O)NR_(a)R_(b)—,—R_(a)NR_(b)R_(c), —R_(a)OR_(b)—, —SR_(a), —SOR_(a) and —SO₂R_(a),wherein R_(a), R_(b) and R_(c) is independently selected from the groupconsisting of hydrogen, C₁₋₈ alkyl, C₃₋₈ cycloalkyl, C₅₋₆ aryl, C₇₋₁₅arylalkyl, C₂₋₁₀ heterocyclyl, C₁₋₆ heteroaryl, and C₂₋₁₂heteroarylalkyl with heteroatoms selected from N, O, S;wherein C₇₋₁₂ arylalkoxy, C₁₋₈ alkyl, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₂₋₁₀heterocyclyl, C₃₋₈ cycloalkyl, is optionally substituted with one ormore of the groups selected from hydrogen, C₁₋₆ alkyl, C₅₋₆ aryl, C₁₋₆heteroaryl, C₂₋₁₀ heterocyclyl, oxo (═O), C₃₋₈ cycloalkyl, halogen, OH,amino, and cyano;R₃ is selected from the group consisting of hydrogen, substituted orunsubstituted C₁₋₈ alkyl, and C₅₋₆ aryl;R₂ is selected from the group consisting of —OR₇, aniline, amino C₅₋₆aryl, and amino C₁₋₆ heteroaryl,wherein aniline, amino C₅₋₆ aryl, and amino C₁₋₆ heteroaryl, isoptionally substituted with one or more of the groups selected from C₁₋₈alkyl, halogen, OH, amino, and cyano;R₇ is selected from the group consisting of hydrogen, C₁₋₈ alkyl, C₅₋₆aryl, C₂₋₁₀ heterocyclyl and —COR₈, wherein R₈ is selected from thegroup consisting of C₁₋₈ alkyl, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₃₋₈cycloalkyl, and C₂₋₁₀ heterocyclyl.

In another embodiment, the invention provides compound of Formula I

their analogs, tautomeric forms, stereoisomers, polymorphs, solvates,intermediates, pharmaceutically acceptable salts, metabolites, andprodrugs thereof;whereinAr is selected from the group consisting of substituted or unsubstitutedC₅₋₆ aryl, C₁₋₆ heteroaryl, and C₂₋₁₀ heterocyclyl with heteroatomsselected from N, O, S;W represents a bond or CR₄R₅, whereinR₄ and R₅ are independently selected from the group consisting ofhydrogen, and substituted or unsubstituted C₁₋₈ alkyl;Y is a bond or is selected from the group consisting of substituted orunsubstituted C₁₋₈ alkyl, C₁₋₈ alkenyl, C₁₋₈ alkynyl, C₅₋₆ aryl, C₁₋₆heteroaryl, C₂₋₁₀ heterocyclcyl, C₃₋₈ cycloalkyl, —CO—, and —CO—C₂₋₁₀heterocyclyl;wherein C₁₋₈ alkyl, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₂₋₁₀ heterocyclyl, C₃₋₈cycloalkyl, is optionally substituted with one or more of the groupsselected from hydrogen, C₁₋₆ alkyl, oxo (═O), C₃₋₈ cycloalkyl, halogen,OH, and cyano;Z represents a bond or is selected from the group consisting of C₁₋₈alkyl, C₁₋₈ alkenyl, C₁₋₈ alkynyl, C₇₋₁₂ alkylaryl, C₇₋₁₂ alkenylaryl,C₇₋₁₅ arylalkenyl, C₂₋₁₂ alkylheteroaryl, —CO—C₇₋₁₂ alkylaryl, —CO—C₇₋₁₂alkenylaryl, —CONR₆—C₁₋₈ alkyl, —NR₆CO—C₁₋₈ alkyl-, —NR₆—C₁₋₈ alkyl,—O—C₁₋₈ alkyl-, —CONR₆—C₅₋₆ aryl-, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₂₋₁₀heterocyclyl, —CO—C₂₋₁₀ heterocyclyl, —NR₆—CO—OC₁₋₈ alkyl, O—CO—NR₆—C₁₋₈alkyl, —NR₆CO—C₅₋₆ aryl-, —NR₆—C₅₋₆ aryl, —NR₆—C₁₋₆ heteroaryl, —C₁₋₈alkyl-O—C₅₋₆ aryl, —O—C₅₋₆ aryl, O—C₁₋₆ heteroaryl, —NR₆—CO—OC₅₋₆ aryl,—CONR₆—C₇₋₁₂ alkylaryl, —CONR₆—C₇₋₁₂ alkenylaryl, —SO₂—C₅₋₆ aryl,—SO₂—C₇₋₁₂ alkylaryl, —NR₆SO₂—C₇₋₁₂ alkylaryl, C₁₋₈ alkyl-CONR₆—C₅₋₆aryl, and O—CO—NR₆—C₅₋₆aryl;R₆ is selected from the group consisting of hydrogen, C₁₋₈ alkyl, C₁₋₆haloalkyl, C₃₋₈ cycloalkyl, C₅₋₆ aryl, and C₁₋₆ heteroaryl, withheteroatoms selected from N, O, S;R₁ is selected from the group consisting of hydrogen, halogen, hydroxy,nitro, cyano, azido, nitroso, oxo (═O), thioxo (═S), —SO₂—, amino,hydrazino, formyl, C₁₋₈ alkyl, C₁₋₈ haloalkyl, C₁₋₈ alkoxy, C₁₋₈haloalkoxy, C₇₋₁₂ arylalkoxy, C₃₋₈ cycloalkyl, C₃₋₈ cycloalkyloxy, C₅₋₆aryl, C₂₋₁₀ heterocyclyl, C₁₋₆ heteroaryl, alkylamino, —COOR_(a),—C(O)R_(b), —C(S)R_(a), —C(O)NR_(a)R_(b), —C(S)NR_(a)R_(b),—NR_(a)C(O)NR_(b)R_(c), NR_(a)C(S)NR_(b)R_(c), —N(R_(a))SOR_(b),—N(R_(a))SO₂R_(b), —NR_(a)C(O)OR_(b), —NR_(a)R_(b), —NR_(a)C(O)R_(b)—,NR_(a)C(S)R_(b)—, —SONR_(a)R_(b)—, —SO₂NR_(a)R_(b)—, —OR_(a),—OR_(a)C(O)OR_(b)—, —OC(O)NR_(a)R_(b), OC(O)R_(a), —OC(O)NR_(a)R_(b)—,—R_(a)NR_(b)R_(c), —R_(a)OR_(b)—, —SR_(a), —SOR_(a) and —SO₂R_(a),wherein R_(a), R_(b) and R_(c) is independently selected from the groupconsisting of hydrogen, C₁₋₈ alkyl, C₃₋₈ cycloalkyl, C₅₋₆ aryl, C₇₋₁₅arylalkyl, C₂₋₁₀ heterocyclyl, C₁₋₆ heteroaryl, and C₂₋₁₂ hetroarylalkylwith heteroatoms selected from N, O, S;wherein C₇₋₁₂ arylalkoxy, C₁₋₈ alkyl, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₂₋₁₀heterocyclcyl, C₃₋₈ cycloalkyl, is optionally substituted with one ormore of the groups selected from hydrogen, C₁₋₆ alkyl, C₅₋₆ aryl, C₁₋₆heteroaryl, C₂₋₁₀ heterocyclcyl, oxo (═O), C₃₋₈ cycloalkyl, halogen, OH,amino, and cyano;R₃ is selected from the group consisting of hydrogen, and substituted orunsubstituted C₁₋₈ alkyl;R₂ is selected from the group consisting of —OR₇, aniline, amino C₅₋₆aryl, and amino C₁₋₆ heteroaryl,wherein aniline, amino C₅₋₆ aryl, and amino C₁₋₆ heteroaryl, isoptionally substituted with one or more of the groups selected from C₁₋₈alkyl, halogen, OH, amino, and cyano;R₇ is selected from the group consisting of hydrogen, C₁₋₈ alkyl, C₅₋₆aryl, C₂₋₁₀ heterocyclyl and —COR₈, wherein R₈ is selected the groupconsisting of C₁₋₈ alkyl, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₃₋₈cycloalkyl,and C₂₋₁₀ heterocyclyl.

In yet another embodiment, the invention relates to compound of FormulaI

their analogs, tautomeric forms, stereoisomers, polymorphs, solvates,intermediates, pharmaceutically acceptable salts, metabolites, andprodrugs thereof;whereinAr is selected from the group consisting of C₅₋₆ aryl, and C₂₋₁₀heterocyclyl with heteroatoms selected from N, O, S;W represents a bond or CR₄R₅, whereinR₄ and R₅ are independently selected from the group consisting ofhydrogen, and substituted or unsubstituted C₁₋₈ alkyl;Y is a bond or is selected from the group consisting of substituted orunsubstituted C₁₋₈ alkyl, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₂₋₁₀heterocyclyl, C₃₋₈ cycloalkyl, —CO—, and —CO—C₂₋₁₀ heterocyclyl;wherein C₁₋₈ alkyl, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₂₋₁₀ heterocyclcyl,C₃₋₈ cycloalkyl, is optionally substituted with one or more of thegroups selected from hydrogen, C₁₋₆ alkyl, oxo (═O), C₃₋₈ cycloalkyl,halogen, OH, and cyano;Z represents a bond or is selected from the group consisting of C₁₋₈alkyl, C₁₋₈ alkenyl, C₁₋₈ alkynyl, C₇₋₁₂ alkylaryl, C₇₋₁₂ alkenylaryl,C₇₋₁₅ arylalkenyl, C₂₋₁₂ alkylheteroaryl, —CO—C₇₋₁₂ alkylaryl, —CO—C₇₋₁₂alkenylaryl, —CONR₆—C₁₋₈ alkyl, —NR₆CO—C₁₋₈ alkyl-, —NR₆—C₁₋₈ alkyl,—O—C₁₋₈ alkyl-, —CONR₆—C₅₋₆ aryl-, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₂₋₁₀heterocyclyl, —CO—C₂₋₁₀ heterocyclyl, —NR₆—CO—OC₁₋₈ alkyl, O—CO—NR₆—C₁₋₈alkyl, —NR₆CO—C₅₋₆ aryl-, —NR₆—C₅₋₆ aryl, —NR₆—C₁₋₆ heteroaryl, —C₁₋₈alkyl-O—C₅₋₆ aryl, —O—C₅₋₆ aryl, O—C₁₋₆ heteroaryl, —NR₆—CO—OC₅₋₆ aryl,—CONR₆—C₇₋₁₂ alkylaryl, —CONR₆—C₇₋₁₂ alkenylaryl, —SO₂—C₅₋₆ aryl,—SO₂—C₇₋₁₂ alkylaryl, —NR₆SO₂—C₇₋₁₂ alkylaryl, C₁₋₈ alkyl-CONR₆—C₅₋₆aryl or O—CO—NR₆—C₅₋₆ aryl;R₆ is selected from the group consisting of hydrogen, C₁₋₈ alkyl, C₁₋₆haloalkyl, C₃₋₈ cycloalkyl, C₅₋₆ aryl, and C₁₋₆ heteroaryl, withheteroatoms selected from N, O, S;R₁ is selected from the group consisting of hydrogen, halogen, hydroxy,nitro, cyano, azido, nitroso, oxo (═O), thioxo (═S), —SO₂—, amino,hydrazino, formyl, C₁₋₈ alkyl, C₁₋₈ haloalkyl, C₁₋₈ alkoxy, C₁₋₈haloalkoxy, C₇₋₁₂ arylalkoxy, C₃₋₈ cycloalkyl, C₃₋₈ cycloalkyloxy, C₅₋₆aryl, C₂₋₁₀ heterocyclyl, C₁₋₆ heteroaryl, alkylamino, —COOR_(a),—C(O)R_(b), —C(S)R_(a), —C(O)NR_(a)R_(b), —C(S)NR_(a)R_(b),—NR_(a)C(O)NR_(b)R_(c), NR_(a)C(S)NR_(b)R_(c), —N(R_(a))SOR_(b),—N(R_(a))SO₂R_(b), —NR_(a)C(O)OR_(b), —NR_(a)R_(b), —NR_(a)C(O)R_(b)—,NR_(a)C(S)R_(b)—, —SONR_(a)R_(b)—, —SO₂NR_(a)R_(b)—, —OR_(a),—OR_(a)C(O)OR_(b)—, —OC(O)NR_(a)R_(b), OC(O)R_(a), —OC(O)NR_(a)R_(b)—,—R_(a)NR_(b)R_(c), —R_(a)OR_(b)—, —SR_(a), —SOR_(a) and —SO₂R_(a),wherein R_(a), R_(b) and R_(c) is independently selected from the groupconsisting of hydrogen, C₁₋₈ alkyl, C₃₋₈ cycloalkyl, C₅₋₆ aryl, C₇₋₁₅arylalkyl, C₂₋₁₀ heterocyclyl, C₁₋₆ heteroaryl, and C₂₋₁₂heteroarylalkyl with heteroatoms selected from N, O, S;wherein C₇₋₁₂ arylalkoxy, C₁₋₈ alkyl, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₂₋₁₀heterocyclcyl, C₃₋₈ cycloalkyl, is optionally substituted with one ormore of the groups selected from hydrogen, C₁₋₆ alkyl, C₅₋₆ aryl, C₁₋₆heteroaryl, C₂₋₁₀ heterocyclcyl, oxo (═O), C₃₋₈ cycloalkyl, halogen, OH,amino, and cyano;R₃ is selected from the group consisting of hydrogen, substituted orunsubstituted C₁₋₈ alkyl, and C₅₋₆ aryl;R₂ is selected from the group consisting of —OR₇, aniline, amino C₅₋₆aryl, and amino C₁₋₆ heteroaryl;wherein aniline, amino C₅₋₆ aryl, and amino C₁₋₆ heteroaryl, isoptionally substituted with one or more of the groups selected from C₁₋₈alkyl, halogen, OH, amino, and cyano;R₇ is selected from the group consisting of hydrogen, C₁₋₈ alkyl, C₅₋₆aryl, C₂₋₁₀ heterocyclyl and —COR₈, wherein R₈ is selected the groupconsisting of C₁₋₈ alkyl, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₃₋₈ cycloalkyl,and C₂₋₁₀ heterocyclyl.

In an embodiment of the present invention, there is provided compound ofFormula I

their analogs, tautomeric forms, stereoisomers, polymorphs, solvates,intermediates, pharmaceutically acceptable salts, metabolites, andprodrugs thereof;whereinAr is selected from the group consisting of substituted or unsubstitutedC₅₋₆ aryl, C₁₋₆ heteroaryl, and C₂₋₁₀ heterocyclyl with heteroatomsselected from N, O, S;W represents a bond or CR₄R₅, whereinR₄ and R₅ is hydrogen;Y is a bond or is selected from the group consisting of substituted orunsubstituted C₁₋₈ alkyl, C₁₋₈ alkenyl, C₁₋₈ alkynyl, C₅₋₆ aryl, C₁₋₆heteroaryl, C₂₋₁₀ heterocyclyl, C₃₋₈ cycloalkyl, —CO—, and —CO—C₂₋₁₀heterocyclyl;wherein C₁₋₈ alkyl, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₂₋₁₀ heterocyclyl, C₃₋₈cycloalkyl, is optionally substituted with one or more of the groupsselected from hydrogen, C₁₋₆ alkyl, oxo (═O), C₃₋₈ cycloalkyl, halogen,OH, and cyano;Z represents a bond or is selected from the group consisting of C₁₋₈alkyl, C₁₋₈ alkenyl, C₁₋₈ alkynyl, C₇₋₁₂ alkylaryl, C₇₋₁₂ alkenylaryl,C₇₋₁₅ arylalkenyl, C₂₋₁₂ alkylheteroaryl, —CO—C₇₋₁₂ alkylaryl, —CO—C₇₋₁₂alkenylaryl, —CONR₆—C₁₋₈ alkyl, —NR₆CO—C₁₋₈ alkyl-, —NR₆—C₁₋₈ alkyl,—O—C₁₋₈ alkyl-, —CONR₆—C₅₋₆ aryl-, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₂₋₁₀heterocyclycl, —CO—C₂₋₁₀ heterocyclyl, —NR₆—CO—OC₁₋₈ alkyl,O—CO—NR₆—C₁₋₈ alkyl, —NR₆CO—C₅₋₆ aryl-, —NR₆—C₅₋₆ aryl, —NR₆—C₁₋₆heteroaryl, —C₁₋₈alkyl-O—C₅₋₆ aryl, —O—C₅₋₆ aryl, O—C₁₋₆ heteroaryl,—NR₆—CO—OC₅₋₆ aryl, —CONR₆—C₇₋₁₂ alkylaryl, —CONR₆—C₇₋₁₂ alkenylaryl,—SO₂—C₅₋₆ aryl, —SO₂—C₇₋₁₂ alkylaryl, —NR₆SO₂—C₇₋₁₂ alkylaryl, C₁₋₈alkyl-CONR₆—C₅₋₆ aryl or O—CO—NR₆—C₅₋₆ aryl;R₆ is selected from the group consisting of hydrogen, C₁₋₈ alkyl, C₁₋₆haloalkyl, C₃₋₈ cycloalkyl, C₅₋₆ aryl, and C₁₋₆ heteroaryl, withheteroatoms selected from N, O, S;R₁ is selected from the group consisting of hydrogen, halogen, C₁₋₈alkyl, C₁₋₈ haloalkyl, C₁₋₈ alkoxy, C₁₋₈ haloalkoxy, C₇₋₁₂ arylalkoxy,C₃₋₈ cycloalkyl, C₃₋₈ cycloalkyloxy, C₅₋₆ aryl, C₂₋₁₀ heterocyclyl, C₁₋₆heteroaryl, —C(O)R_(b), —C(O)NR_(a)R_(b), wherein R_(a), and R_(b) isindependently selected from the group consisting of hydrogen, C₁₋₈alkyl, and C₅₋₆ aryl; wherein C₇₋₁₂ arylalkoxy, C₁₋₈ alkyl, C₅₋₆ aryl,C₁₋₆ heteroaryl, C₂₋₁₀ heterocyclcyl, C₃₋₈ cycloalkyl, is optionallysubstituted with one or more of the groups selected from hydrogen, C₁₋₆alkyl, C₅₋₆ aryl, oxo (═O), halogen, OH, amino, and cyano;R₃ is hydrogen;R₂ is selected from the group consisting of —OR₇, aniline, amino C₅₋₆aryl, and amino C₁₋₆ heteroaryl,wherein aniline, amino C₅₋₆ aryl, and amino C₁₋₆ heteroaryl, isoptionally substituted with one or more of the groups selected from C₁₋₈alkyl, halogen, OH, amino, and cyano;R₇ is selected from the group consisting of hydrogen, C₁₋₈alkyl,C₅₋₆aryl, C₂₋₁₀ heterocyclyl and —COR₈, wherein R₈ is selected the groupconsisting of C₁₋₈ alkyl, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₃₋₈ cycloalkyl,and C₂₋₁₀ heterocyclyl.

In another embodiment, the invention relates to compound of Formula I

their analogs, tautomeric forms, stereoisomers, polymorphs, solvates,intermediates, pharmaceutically acceptable salts, metabolites, andprodrugs thereof;whereinAr is selected from the group consisting of C₅₋₆ aryl, and C₂₋₁₀heterocyclyl with heteroatoms selected from N, O, S;W represents a bond or CR₄R₅, whereinR₄ and R₅ is hydrogen;Y is a bond or is selected from the group consisting of substituted orunsubstituted C₁₋₈ alkyl, C₁₋₈ alkenyl, C₁₋₈ alkynyl, C₅₋₆ aryl, C₁₋₆heteroaryl, C₂₋₁₀ heterocyclcyl, C₃₋₈ cycloalkyl, —CO—, and —CO—C₂₋₁₀heterocyclyl;wherein C₁₋₈ alkyl, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₂₋₁₀ heterocyclyl, C₃₋₈cycloalkyl, is optionally substituted with one or more of the groupsselected from hydrogen, C₁₋₆ alkyl, oxo (═O), C₃₋₈ cycloalkyl, halogen,OH, and cyano;Z represents a bond or is selected from the group consisting of C₁₋₈alkyl, C₁₋₈ alkenyl, C₇₋₁₂ alkylaryl, C₇₋₁₅ arylalkenyl, C₂₋₁₂alkylheteroaryl, —CO— C₇₋₁₂alkylaryl, —CO— C₇₋₁₂alkenylaryl, —CONR₆—C₁₋₈alkyl, C₅₋₆aryl, C₁₋₆heteroaryl, —CO—C₂₋₁₀ heterocyclyl, —NR₆—C₅₋₆aryl, —NR₆—C₁₋₆heteroaryl, —O—C₅₋₆ aryl, O—C₁₋₆ heteroaryl, —CONR₆—C₇₋₁₂alkylaryl, —SO₂—C₅₋₆ aryl, —SO₂—C₇₋₁₂ alkylaryl, and —NR₆SO₂—C₇₋₁₂alkylaryl;R₆ is selected from the group consisting of hydrogen, and C₁₋₈ alkyl;R₁ is selected from the group consisting of hydrogen, halogen, hydroxy,nitro, cyano, azido, nitroso, oxo (═O), thioxo (═S), —SO₂—, amino,hydrazino, formyl, C₁₋₈ alkyl, C₁₋₈ haloalkyl, C₁₋₈ alkoxy, C₁₋₈haloalkoxy, C₇₋₁₂ arylalkoxy, C₃₋₈ cycloalkyl, C₃₋₈ cycloalkyloxy, C₅₋₆aryl, C₂₋₁₀ heterocyclyl, C₁₋₆ heteroaryl, alkylamino, —COOR_(a),—C(O)R_(b), —C(S)R_(a), —C(O)NR_(a)R_(b), —C(S)NR_(a)R_(b),—NR_(a)C(O)NR_(b)R_(c), NR_(a)C(S)NR_(b)R_(c), —N(R_(a))SOR_(b),—N(R_(a))SO₂R_(b), —NR_(a)C(O)OR_(b), —NR_(a)R_(b), —NR_(a)C(O)R_(b)—,NR_(a)C(S)R_(b)—, —SONR_(a)R_(b)—, —SO₂NR_(a)R_(b)—, —OR_(a),—OR_(a)C(O)OR_(b)—, —OC(O)NR_(a)R_(b), OC(O)R_(a), —OC(O)NR_(a)R_(b)—,—R_(a)NR_(b)R_(c), —R_(a)OR_(b)—, —SR_(a), —SOR_(a) and —SO₂R_(a),wherein R_(a), R_(b) and R_(c) is independently selected from the groupconsisting of hydrogen, C₁₋₈ alkyl, C₃₋₈ cycloalkyl, C₅₋₆ aryl, C₇₋₁₅arylalkyl, C₂₋₁₀ heterocyclyl, C₁₋₆ heteroaryl, and C₂₋₁₂heteroarylalkyl with heteroatoms selected from N, O, S;wherein C₇₋₁₂ arylalkoxy, C₁₋₈ alkyl, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₂₋₁₀heterocyclcyl, C₃₋₈ cycloalkyl, is optionally substituted with one ormore of the groups selected from hydrogen, C₁₋₆ alkyl, C₅₋₆ aryl, C₁₋₆heteroaryl, C₂₋₁₀ heterocyclyl, oxo (═O), C₃₋₈ cycloalkyl, halogen, OH,amino, and cyano;R₃ is selected from the group consisting of hydrogen, substituted orunsubstituted C₁₋₈ alkyl, and C₅₋₆ aryl;R₂ is selected from the group consisting of —OR₇, aniline, amino C₅₋₆aryl, and amino C₁₋₆ heteroaryl,wherein aniline, amino C₅₋₆ aryl, and amino C₁₋₆ heteroaryl, isoptionally substituted with one or more of the groups selected from C₁₋₈alkyl, halogen, OH, amino, and cyano;R₇ is selected from the group consisting of hydrogen, C₁₋₈ alkyl, C₅₋₆aryl, C₂₋₁₀ heterocyclyl and —COR₈, wherein R₈ is selected the groupconsisting of C₁₋₈ alkyl, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₃₋₈ cycloalkyl,and C₂₋₁₀ heterocyclyl.

In yet another embodiment, the invention relates to compound of FormulaI

their analogs, tautomeric forms, stereoisomers, polymorphs, solvates,intermediates, pharmaceutically acceptable salts, metabolites, andprodrugs thereof;whereinAr is selected from the group consisting of C₅₋₆ aryl, and C₂₋₁₀heterocyclyl with heteroatoms selected from N, O, S;W represents a bond or CR₄R₅, whereinR₄ and R₅ is hydrogen;Y is a bond or is selected from the group consisting of substituted orunsubstituted C₁₋₈ alkyl, C₁₋₈ alkenyl, C₁₋₈ alkynyl, C₅₋₆ aryl, C₁₋₆heteroaryl, C₂₋₁₀ heterocyclyl, C₃₋₈ cycloalkyl, —CO—, and —CO—C₂₋₁₀heterocyclyl;wherein C₁₋₈ alkyl, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₂₋₁₀ heterocyclyl, C₃₋₈cycloalkyl, is optionally substituted with one or more of the groupsselected from hydrogen, C₁₋₆ alkyl, oxo (═O), C₃₋₈ cycloalkyl, halogen,OH, and cyano;Z represents a bond or is selected from the group consisting of C₁₋₈alkyl, C₁₋₈ alkenyl, C₇₋₁₂ alkylaryl, C₇₋₁₅ arylalkenyl, C₂₋₁₂alkylheteroaryl, —CO—C₇₋₁₂ alkylaryl, —CO—C₇₋₁₂ alkenylaryl, —CONR₆—C₁₋₈alkyl, C₅₋₆ aryl, C₁₋₆ heteroaryl, —CO—C₂₋₁₀ heterocyclyl, —NR₆—C₅₋₆aryl, —NR₆— C₁₋₆ heteroaryl, —O—C₅₋₆ aryl, —O—C₁₋₆ heteroaryl,—CONR₆—C₇₋₁₂ alkylaryl, —SO₂—C₅₋₆ aryl, —SO₂—C₇₋₁₂ alkylaryl, and—NR₆SO₂—C₇₋₁₂ alkylaryl;R₆ is selected from the group consisting of hydrogen, and C₁₋₈ alkyl;R₁ is selected from the group consisting of hydrogen, halogen, C₁₋₈alkyl, C₁₋₈ haloalkyl, C₁₋₈ alkoxy, C₁₋₈ haloalkoxy, C₇₋₁₂ arylalkoxy,C₃₋₈ cycloalkyl, C₃₋₈ cycloalkyloxy, C₅₋₆ aryl, C₂₋₁₀ heterocyclyl, C₁₋₆heteroaryl, —C(O)R_(b), —C(O)NR_(a)R_(b), wherein R_(a), and R_(b) isindependently selected from the group consisting of hydrogen, C₁₋₈alkyl, and C₅₋₆ aryl; wherein C₇₋₁₂ arylalkoxy, C₁₋₈ alkyl, C₅₋₆ aryl,C₁₋₆ heteroaryl, C₂₋₁₀ heterocyclyl, C₃₋₈ cycloalkyl, is optionallysubstituted with one or more of the groups selected from hydrogen, C₁₋₆alkyl, C₅₋₆ aryl, oxo (═O), halogen, OH, amino, and cyano;R₃ is selected from the group consisting of hydrogen, substituted orunsubstituted C₁₋₈ alkyl, and C₅₋₆ aryl;R₂ is selected from the group consisting of —OR₇, aniline, amino C₅₋₆aryl, and amino C₁₋₆ heteroaryl,wherein aniline, amino C₅₋₆ aryl, and amino C₁₋₆ heteroaryl, isoptionally substituted with one or more of the groups selected from C₁₋₈alkyl, halogen, OH, amino, and cyano;R₇ is selected from the group consisting of hydrogen, C₁₋₈ alkyl, C₅₋₆aryl, C₂₋₁₀ heterocyclyl and —COR₈, wherein R₈ is selected the groupconsisting of C₁₋₈ alkyl, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₃₋₈ cycloalkyl,and C₂₋₁₀ heterocyclyl.

In an embodiment, there is provided compound of Formula I

their analogs, tautomeric forms, stereoisomers, polymorphs, solvates,intermediates, pharmaceutically acceptable salts, metabolites, andprodrugs thereof;whereinAr is selected from the group consisting of C₅₋₆ aryl, and C₂₋₁₀heterocyclyl with heteroatoms selected from N, O, S;W represents a bond or CR₄R₅, whereinR₄ and R₅ is hydrogen;Y is a bond or is selected from the group consisting of substituted orunsubstituted C₁₋₈ alkyl, C₁₋₈ alkenyl, C₁₋₈ alkynyl, C₅₋₆ aryl, C₁₋₆heteroaryl, C₂₋₁₀ heterocyclyl, C₃₋₈ cycloalkyl, —CO—, and —CO—C₂₋₁₀heterocyclyl;wherein C₁₋₈ alkyl, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₂₋₁₀ heterocyclyl, C₃₋₈cycloalkyl, is optionally substituted with one or more of the groupsselected from hydrogen, C₁₋₆ alkyl, oxo (═O), C₃₋₈ cycloalkyl, halogen,OH, and cyano;Z represents a bond or is selected from the group consisting of C₁₋₈alkyl, C₁₋₈ alkenyl, C₇₋₁₂ alkylaryl, C₇₋₁₅ arylalkenyl, C₂₋₁₂alkylheteroaryl, —CO—C₇₋₁₂ alkylaryl, —CO—C₇₋₁₂ alkenylaryl, —CONR₆—C₁₋₈alkyl, C₅₋₆ aryl, C₁₋₆ heteroaryl, —CO—C₂₋₁₀ heterocyclyl, —NR₆—C₅₋₆aryl, —NR₆—C₁₋₆ heteroaryl, —O—C₅₋₆ aryl, —O—C₁₋₆ heteroaryl,—CONR₆—C₇₋₁₂ alkylaryl, —SO₂—C₅₋₆ aryl, —SO₂—C₇₋₁₂ alkylaryl, and—NR₆SO₂—C₇₋₁₂ alkylaryl;R₆ is selected from the group consisting of hydrogen, and C₁₋₈ alkyl;R₁ is selected from the group consisting of hydrogen, halogen, hydroxy,nitro, cyano, azido, nitroso, oxo (═O), thioxo (═S), —SO₂—, amino,hydrazino, formyl, C₁₋₈ alkyl, C₁₋₈ haloalkyl, C₁₋₈ alkoxy, C₁₋₈haloalkoxy, C₇₋₁₂ arylalkoxy, C₃₋₈ cycloalkyl, C₃₋₈ cycloalkyloxy, C₅₋₆aryl, C₂₋₁₀ heterocyclyl, C₁₋₆ heteroaryl, alkylamino, —COOR_(a),—C(O)R_(b), —C(S)R_(a), —C(O)NR_(a)R_(b), —C(S)NR_(a)R_(b),—NR_(a)C(O)NR_(b)R_(c), —NR_(a)C(S)NR_(b)R_(c), —N(R_(a))SOR_(b),—N(R_(a))SO₂R_(b), —NR_(a)C(O)OR_(b), —NR_(a)R_(b), —NR_(a)C(O)R_(b)—,NR_(a)C(S)R_(b)—, —SONR_(a)R_(b)—, —SO₂NR_(a)R_(b)—, —OR_(a),—OR_(a)C(O)OR_(b)—, —OC(O)NR_(a)R_(b), OC(O)R_(a), —OC(O)NR_(a)R_(b)—,—R_(a)NR_(b)R_(c), —R_(a)OR_(b)—, —SR_(a), —SOR_(a) and —SO₂R_(a),wherein R_(a), R_(b) and R_(c) is independently selected from the groupconsisting of hydrogen, C₁₋₈ alkyl, C₃₋₈ cycloalkyl, C₅₋₆ aryl, C₇₋₁₅arylalkyl, C₂₋₁₀ heterocyclyl, C₁₋₆ heteroaryl, and C₂₋₁₂heteroarylalkyl with heteroatoms selected from N, O, S;wherein C₇₋₁₂ arylalkoxy, C₁₋₈ alkyl, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₂₋₁₀heterocyclyl, C₃₋₈ cycloalkyl, is optionally substituted with one ormore of the groups selected from hydrogen, C₁₋₆ alkyl, C₅₋₆ aryl, C₁₋₆heteroaryl, C₂₋₁₀ heterocyclyl, oxo (═O), C₃₋₈ cycloalkyl, halogen, OH,amino, and cyano;R₃ is hydrogen;R₂ is selected from the group consisting of —OR₇, and aniline;wherein aniline is optionally substituted with one or more of the groupsselected from C₁₋₈ alkyl, halogen, OH, amino, and cyano;R₇ is selected from the group consisting of hydrogen, and C₁₋₈ alkyl.

In another embodiment, the invention relates to compound of Formula I

their analogs, tautomeric forms, stereoisomers, polymorphs, solvates,intermediates, pharmaceutically acceptable salts, metabolites, andprodrugs thereof;whereinAr is selected from the group consisting of C₅₋₆ aryl, and C₂₋₁₀heterocyclyl with heteroatoms selected from N, O, S;W represents a bond or CR₄R₅, whereinR₄ and R₅ is hydrogen;Y is a bond or is selected from the group consisting of substituted orunsubstituted C₁₋₈ alkyl, C₁₋₈ alkenyl, C₁₋₈ alkynyl, C₅₋₆ aryl, C₁₋₆heteroaryl, C₂₋₁₀ heterocyclyl, C₃₋₈ cycloalkyl, —CO—, and —CO—C₂₋₁₀heterocyclyl;wherein C₁₋₈ alkyl, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₂₋₁₀ heterocyclyl, C₃₋₈cycloalkyl, is optionally substituted with one or more of the groupsselected from hydrogen, C₁₋₆ alkyl, oxo (═O), C₃₋₈ cycloalkyl, halogen,OH, and cyano;Z represents a bond or is selected from the group consisting of C₁₋₈alkyl, C₁₋₈ alkenyl, C₇₋₁₂ alkylaryl, C₇₋₁₅ arylalkenyl, C₂₋₁₂alkylheteroaryl, —CO—C₇₋₁₂ alkylaryl, —CO—C₇₋₁₂ alkenylaryl, —CONR₆—C₁₋₈alkyl, C₅₋₆ aryl, C₁₋₆ heteroaryl, —CO—C₂₋₁₀ heterocyclyl, —NR₆—C₅₋₆aryl, —NR₆—C₁₋₆ heteroaryl, —O—C₅₋₆ aryl, —O—C₁₋₆ heteroaryl,—CONR₆—C₇₋₁₂ alkylaryl, —SO₂—C₅₋₆ aryl, —SO₂—C₇₋₁₂ alkylaryl, and—NR₆SO₂—C₇₋₁₂ alkylaryl;R₆ is selected from the group consisting of hydrogen, and C₁₋₈ alkyl;R₁ is selected from the group consisting of hydrogen, halogen, hydroxy,nitro, cyano, azido, nitroso, oxo (═O), thioxo (═S), —SO₂—, amino,hydrazino, formyl, C₁₋₈ alkyl, C₁₋₈ haloalkyl, C₁₋₈ alkoxy, C₁₋₈haloalkoxy, C₇₋₁₂ arylalkoxy, C₃₋₈ cycloalkyl, C₃₋₈ cycloalkyloxy, C₅₋₆aryl, C₂₋₁₀ heterocyclyl, C₁₋₆ heteroaryl, alkylamino, —COOR_(a),—C(O)R_(b), —C(S)R_(a), —C(O)NR_(a)R_(b), —C(S)NR_(a)R_(b),—NR_(a)C(O)NR_(b)R_(c), NR_(a)C(S)NR_(b)R_(c), —N(R_(a))SOR_(b),—N(R_(a))SO₂R_(b), —NR_(a)C(O)OR_(b), —NR_(a)R_(b), —NR_(a)C(O)R_(b)—,NR_(a)C(S)R_(b)—, —SONR_(a)R_(b)—, —SO₂NR_(a)R_(b)—, —OR_(a),—OR_(a)C(O)OR_(b)—, —OC(O)NR_(a)R_(b), OC(O)R_(a), —OC(O)NR_(a)R_(b)—,—R_(a)NR_(b)R_(c), —R_(a)OR_(b)—, —SR_(a), —SOR_(a) and —SO₂R_(a),wherein R_(a), R_(b) and R_(c) is independently selected from the groupconsisting of hydrogen, C₁₋₈ alkyl, C₃₋₈ cycloalkyl, C₅₋₆ aryl, C₇₋₁₅arylalkyl, C₂₋₁₀ heterocyclyl, C₁₋₆ heteroaryl, and C₂₋₁₂ hetroarylalkylwith heteroatoms selected from N, O, S;wherein C₇₋₁₂ arylalkoxy, C₁₋₈ alkyl, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₂₋₁₀heterocyclyl, C₃₋₈ cycloalkyl, is optionally substituted with one ormore of the groups selected from hydrogen, C₁₋₆ alkyl, C₅₋₆ aryl, C₁₋₆heteroaryl, C₂₋₁₀ heterocyclyl, oxo (═O), C₃₋₈ cycloalkyl, halogen, OH,amino, and cyano;R₃ is hydrogen;R₂ is selected from the group consisting of —OR₇, and aniline;wherein aniline is optionally substituted with one or more of the groupsselected from C₁₋₈ alkyl, halogen, OH, amino, and cyano.

In yet another embodiment, the invention relates to compound of FormulaI

their analogs, tautomeric forms, stereoisomers, polymorphs, solvates,intermediates, pharmaceutically acceptable salts, metabolites, andprodrugs thereof;whereinAr is selected from the group consisting of C₅₋₆ aryl, and C₂₋₁₀heterocyclyl with heteroatoms selected from N, O, S;W represents a bond or CR₄R₅, whereinR₄ and R₅ is hydrogen;Y is a bond or is selected from the group consisting of substituted orunsubstituted C₁₋₈ alkyl, C₁₋₈ alkenyl, C₁₋₈ alkynyl, C₅₋₆ aryl, C₁₋₆heteroaryl, C₂₋₁₀ heterocyclyl, C₃₋₈ cycloalkyl, —CO—, and —CO—C₂₋₁₀heterocyclyl;wherein C₁₋₈ alkyl, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₂₋₁₀ heterocyclyl, C₃₋₈cycloalkyl, is optionally substituted with one or more of the groupsselected from hydrogen, C₁₋₆ alkyl, oxo (═O), C₃₋₈ cycloalkyl, halogen,OH, and cyano;Z represents a bond or is selected from the group consisting of C₁₋₈alkyl, C₁₋₈ alkenyl, C₇₋₁₂-alkylaryl, C₇₋₁₅-arylalkenyl,C₂₋₁₂-alkylheteroaryl, —CO—C₇₋₁₂ alkylaryl, —CO—C₇₋₁₂ alkenylaryl,—CONR₆—C₁₋₈ alkyl, C₅₋₆ aryl, C₁₋₆ heteroaryl, —CO—C₂₋₁₀ heterocyclyl,—NR₆—C₅₋₆ aryl, —NR₆—C₁₋₆ heteroaryl, —O—C₅₋₆ aryl, —O—C₁₋₆ heteroaryl,—CONR₆—C₇₋₁₂ alkylaryl, —SO₂—C₅₋₆ aryl, —SO₂—C₇₋₁₂ alkylaryl, and—NR₆SO₂—C₇₋₁₂ alkylaryl;R₆ is selected from the group consisting of hydrogen, and C₁₋₈ alkyl;R₁ is selected from the group consisting of hydrogen, halogen, hydroxy,nitro, cyano, azido, nitroso, oxo (═O), thioxo (═S), —SO₂—, amino,hydrazino, formyl, C₁₋₈ alkyl, C₁₋₈ haloalkyl, C₁₋₈ alkoxy, C₁₋₈haloalkoxy, C₇₋₁₂ arylalkoxy, C₃₋₈ cycloalkyl, C₃₋₈ cycloalkyloxy, C₅₋₆aryl, C₂₋₁₀ heterocyclyl, C₁₋₆ heteroaryl, alkylamino, —COOR_(a),—C(O)R_(b), —C(S)R_(a), —C(O)NR_(a)R_(b), —C(S)NR_(a)R_(b),—NR_(a)C(O)NR_(b)R_(c), NR_(a)C(S)NR_(b)R_(c), —N(R_(a))SOR_(b),—N(R_(a))SO₂R_(b), —NR_(a)C(O)OR_(b), —NR_(a)R_(b), —NR_(a)C(O)R_(b)—,NR_(a)C(S)R_(b)—, —SONR_(a)R_(b)—, —SO₂NR_(a)R_(b)—, —OR_(a),—OR_(a)C(O)OR_(b)—, —OC(O)NR_(a)R_(b), OC(O)R_(a), —OC(O)NR_(a)R_(b)—,—R_(a)NR_(b)R_(c), —R_(a)OR_(b)—, —SR_(a), —SOR_(a) and —SO₂R_(a),wherein R_(a), R_(b) and R_(c) is independently selected from the groupconsisting of hydrogen, C₁₋₈ alkyl, C₃₋₈ cycloalkyl, C₅₋₆ aryl, C₇₋₁₅arylalkyl, C₂₋₁₀ heterocyclyl, C₁₋₆ heteroaryl, and C₂₋₁₂heteroarylalkyl with heteroatoms selected from N, O, S;wherein C₇₋₁₂ arylalkoxy, C₁₋₈ alkyl, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₂₋₁₀heterocyclyl, C₃₋₈ cycloalkyl, is optionally substituted with one ormore of the groups selected from hydrogen, C₁₋₆ alkyl, C₅₋₆ aryl, C₁₋₆heteroaryl, C₂₋₁₀ heterocyclyl, oxo (═O), C₃₋₈ cycloalkyl, halogen, OH,amino, and cyano;R₃ is hydrogen;R₂ is selected from the group consisting of —OR₇, R₇ is selected fromthe group consisting of hydrogen, and C₁₋₈ alkyl.

In an embodiment of the present invention, there is provided a compoundof Formula I

their analogs, tautomeric forms, stereoisomers, polymorphs, solvates,intermediates, pharmaceutically acceptable salts, metabolites, andprodrugs thereof;whereinAr is selected from the group consisting of C₅₋₆aryl, andC₂₋₁₀heterocyclyl with heteroatoms selected from N, O, S;W represents a bond or CR₄R₅, whereinR₄ and R₅ is hydrogen;Y is a bond or is selected from the group consisting of substituted orunsubstituted C₁₋₈alkyl, C₁₋₈alkenyl, C₁₋₈alkynyl, C₅₋₆aryl,C₁₋₆heteroaryl, C₂₋₁₀heterocyclyl, C₃₋₈cycloalkyl, —CO—, and—CO—C₂₋₁₀heterocyclyl;wherein C₁₋₈alkyl, C₅₋₆aryl, C₁₋₆heteroaryl, C₂₋₁₀heterocyclyl,C₃₋₈cycloalkyl, is optionally substituted with one or more of the groupsselected from hydrogen, C₁₋₆ alkyl, oxo (═O), C₃₋₈ cycloalkyl, halogen,OH, and cyano;Z represents a bond or is selected from the group consisting ofC₁₋₈alkyl, C₁₋₈alkenyl, C₇₋₁₂-alkylaryl, C₇₋₁₅-arylalkenyl,C₂₋₁₂-alkylheteroaryl, —CO—C₇₋₁₂alkylaryl, —CO—C₇₋₁₂alkenylaryl,—CONR₆—C₁₋₈alkyl, C₅₋₆aryl, C₁₋₆heteroaryl, —CO—C₂₋₁₀heterocyclyl,—NR₆—C₅₋₆aryl, —NR₆—C₁₋₆heteroaryl, —O—C₅₋₆aryl, —O—C₁₋₆heteroaryl,—CONR₆—C₇₋₁₂alkylaryl, —SO₂—C₅₋₆aryl, —SO₂—C₇₋₁₂alkylaryl, and—NR₆SO₂—C₇₋₁₂alkylaryl;R₆ is selected from the group consisting of hydrogen, and C₁₋₈ alkyl;R₁ is selected from the group consisting of hydrogen, halogen, hydroxy,nitro, cyano, azido, nitroso, oxo (═O), thioxo (═S), —SO₂—, amino,hydrazino, formyl, C₁₋₈alkyl, C₁₋₈haloalkyl, C₁₋₈alkoxy, C₁₋₈haloalkoxy,C₇₋₁₂arylalkoxy, C₃₋₈cycloalkyl, C₃₋₈cycloalkyloxy, C₅₋₆aryl,C₂₋₁₀heterocyclyl, C₁₋₆heteroaryl, alkylamino, —COOR_(a), —C(O)R_(b),—C(S)R_(a), —C(O)NR_(a)R_(b), —C(S)NR_(a)R_(b), —NR_(a)C(O)NR_(b)R_(c),NR_(a)C(S)NR_(b)R_(c), —N(R_(a))SOR_(b), —N(R_(a))SO₂R_(b),—NR_(a)C(O)OR_(b), —NR_(a)R_(b), —NR_(a)C(O)R_(b)—, NR_(a)C(S)R_(b)—,—SONR_(a)R_(b)—, —SO₂NR_(a)R_(b)—, —OR_(a), —OR_(a)C(O)OR_(b)—,—OC(O)NR_(a)R_(b), OC(O)R_(a), —OC(O)NR_(a)R_(b)—, —R_(a)NR_(b)R_(c),—R_(a)OR_(b)—, —SR_(a), —SOR_(a) and —SO₂R_(a), wherein R_(a), R_(b) andR_(c) is independently selected from the group consisting of hydrogen,C₁₋₈alkyl, C₃₋₈cycloalkyl, C₅₋₆aryl, C₇₋₁₅arylalkyl, C₂₋₁₀heterocyclyl,C₁₋₆heteroaryl, and C₂₋₁₂heteroarylalkyl with heteroatoms selected fromN, O, S;wherein C₇₋₁₂arylalkoxy, C₁₋₈alkyl, C₅₋₆aryl, C₁₋₆heteroaryl,C₂₋₁₀heterocyclyl, C₃₋₈cycloalkyl, is optionally substituted with one ormore of the groups selected from hydrogen, C₁₋₆ alkyl, C₅₋₆aryl,C₁₋₆heteroaryl, C₂₋₁₀heterocyclyl, oxo (═O), C₃₋₈ cycloalkyl, halogen,OH, amino, and cyano;R₃ is hydrogen;R₂ is selected from the group consisting of aniline, amino C₅₋₆aryl, andamino C₁₋₆heteroaryl, wherein aniline, amino C₅₋₆aryl, and aminoC₁₋₆heteroaryl, is optionally substituted with one or more of the groupsselected from C₁₋₈ alkyl, halogen, OH, amino, and cyano.

In an embodiment of the present invention, there is provided a compoundof Formula I

their analogs, tautomeric forms, stereoisomers, polymorphs, solvates,intermediates, pharmaceutically acceptable salts, metabolites, andprodrugs thereof;whereinAr is selected from the group consisting of substituted or unsubstitutedC₅₋₆aryl, C₁₋₆ heteroaryl, and C₂₋₁₀ heterocyclyl with heteroatomsselected from N, O, S;W represents a bond or CR₄R₅, whereinR₄ and R₅ are independently selected from the group consisting ofhydrogen, substituted or unsubstituted C₁₋₈ alkyl, C₅₋₆ aryl, and C₁₋₆heteroaryl with heteroatoms selected from N, O, S;Y is a bond or is selected from the group consisting of substituted orunsubstituted C₁₋₈ alkyl, C₁₋₈ alkenyl, C₁₋₈ alkynyl, C₅₋₆ aryl, C₁₋₆heteroaryl, C₂₋₁₀ heterocyclyl, C₃₋₈ cycloalkyl, —CO—, and —CO—C₂₋₁₀heterocyclyl;wherein C₁₋₈ alkyl, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₂₋₁₀ heterocyclyl, C₃₋₈cycloalkyl, is optionally substituted with one or more of the groupsselected from hydrogen, C₁₋₆ alkyl, oxo (═O), C₃₋₈ cycloalkyl, halogen,OH, and cyano;Z represents a bond or is selected from the group consisting of C₁₋₈alkyl, C₁₋₈ alkenyl, C₁₋₈ alkynyl, C₇₋₁₂-alkylaryl, C₇₋₁₂-alkenylaryl,C₇₋₁₅-arylalkenyl, C₂₋₁₂-alkylheteroaryl, —CO—C₇₋₁₂ alkylaryl, —CO—C₇₋₁₂alkenylaryl, —CONR₆—C₁₋₈ alkyl, —NR₆CO—C₁₋₈ alkyl-, —NR₆—C₁₋₈ alkyl,—O—C₁₋₈ alkyl-, —CONR₆—C₅₋₆ aryl-, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₂₋₁₀heterocyclyl, —CO—C₂₋₁₀ heterocyclyl, —NR₆—CO—OC₁₋₈ alkyl, O—CO—NR₆—C₁₋₈alkyl, —NR₆CO—C₅₋₆ aryl-, —NR₆—C₅₋₆ aryl, —NR₆—C₁₋₆ heteroaryl, —C₁₋₈alkyl-O—C₅₋₆ aryl, —O—C₅₋₆ aryl, O—C₁₋₆ heteroaryl, —NR₆—CO—OC₅₋₆ aryl,—CONR₆—C₇₋₁₂ alkylaryl, —CONR₆—C₇₋₁₂ alkenylaryl, —SO₂—C₅₋₆ aryl,—SO₂—C₇₋₁₂ alkylaryl, —NR₆SO₂—C₇₋₁₂ alkylaryl, C₁₋₈ alkyl-CONR₆—C₅₋₆aryl, and O—CO—NR₆—C₅₋₆ aryl;R₆ is selected from the group consisting of hydrogen, C₁₋₈ alkyl, C₁₋₆haloalkyl, C₃₋₈ cycloalkyl, C₅₋₆ aryl, and C₁₋₆ heteroaryl, withheteroatoms selected from N, O, S;R₁ is selected from the group consisting of hydrogen, halogen hydroxy,nitro, cyano, azido, nitroso, oxo (═O), thioxo (═S), —SO₂—, amino,hydrazino, formyl, C₁₋₈ alkyl, C₁₋₈ haloalkyl, C₁₋₈ alkoxy, C₁₋₈haloalkoxy, C₇₋₁₂ arylalkoxy, C₃₋₈ cycloalkyloxy, C₅₋₆ aryl, C₂₋₁₀heterocyclyl, C₁₋₆ heteroaryl, alkylamino, —COOR_(a), —C(O)R_(b),—C(S)R_(a), —C(O)NR_(a)R_(b), —C(S)NR_(a)R_(b), —NR_(a)C(O)NR_(b)R_(c),NR_(a)C(S)NR_(b)R_(c), —N(R_(a))SOR_(b), —N(R_(a))SO₂R_(b),—NR_(a)C(O)OR_(b), —NR_(a)R_(b), —NR_(a)C(O)R_(b)—, —NR_(a)C(S)R_(b)—,—SONR_(a)R_(b)—, —SO₂NR_(a)R_(b)—, —OR_(a), —OR_(a)C(O)OR_(b)—,—OC(O)NR_(a)R_(b), OC(O)R_(a), —OC(O)NR_(a)R_(b)—, —R_(a)NR_(b)R_(c),—R_(a)OR_(b)—, —SR_(a), —SOR_(a) and —SO₂R_(a), wherein R_(a), R_(b) andR_(c) is independently selected from the group consisting of hydrogen,C₁₋₈ alkyl, C₃₋₈ cycloalkyl, C₅₋₆ aryl, C₇₋₁₅ arylalkyl, C₂₋₁₀heterocyclyl, C₁₋₆ heteroaryl, and C₂₋₁₂ heteroarylalkyl withheteroatoms selected from N, O, S;wherein C₇₋₁₂ arylalkoxy, C₁₋₈ alkyl, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₂₋₁₀heterocyclyl, C₃₋₈ cycloalkyl, is optionally substituted with one ormore of the groups selected from hydrogen, C₁₋₆ alkyl, C₅₋₆ aryl, C₁₋₆heteroaryl, C₂₋₁₀ heterocyclyl, oxo (═O), C₃₋₈ cycloalkyl, halogen, OH,amino, and cyano;R₃ is selected from the group consisting of hydrogen, substituted orunsubstituted C₁₋₈ alkyl, and C₅₋₆ aryl;R₂ is selected from the group consisting of —OR₇, aniline, amino C₅₋₆aryl, and amino C₁₋₆ heteroaryl,wherein aniline, amino C₅₋₆ aryl, and amino C₁₋₆ heteroaryl, isoptionally substituted with one or more of the groups selected from C₁₋₈alkyl, halogen, OH, amino, and cyano;R₇ is selected from the group consisting of hydrogen, C₁₋₈ alkyl, C₅₋₆aryl, C₂₋₁₀ heterocyclyl and —COR₈, wherein R₈ is selected from thegroup consisting of C₁₋₈ alkyl, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₃₋₈cycloalkyl, and C₂₋₁₀ heterocyclyl.

In an embodiment of the present invention, there is provided a compoundof

their analogs, tautomeric forms, stereoisomers, polymorphs, solvates,intermediates, pharmaceutically acceptable salts, metabolites, andprodrugs thereof;whereinAr is selected from the group consisting of substituted or unsubstitutedC₅₋₆aryl, C₁₋₆ heteroaryl, and C₂₋₁₀ heterocyclyl with heteroatomsselected from N, O, S;W represents a bond or CR₄R₅, whereinR₄ and R₅ are independently selected from the group consisting ofhydrogen, substituted or unsubstituted C₁₋₈ alkyl, C₅₋₆ aryl, and C₁₋₆heteroaryl with heteroatoms selected from N, O, S;Y is a bond or is selected from the group consisting of substituted orunsubstituted C₁₋₈ alkyl, C₁₋₈ alkenyl, C₁₋₈ alkynyl, C₅₋₆ aryl, C₁₋₆heteroaryl, C₂₋₁₀ heterocyclyl, C₃₋₈ cycloalkyl, —CO—, and —CO—C₂₋₁₀heterocyclyl;wherein C₁₋₈ alkyl, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₂₋₁₀ heterocyclyl, C₃₋₈cycloalkyl, is optionally substituted with one or more of the groupsselected from hydrogen, C₁₋₆ alkyl, oxo (═O), C₃₋₈ cycloalkyl, halogen,OH, and cyano;Z represents a bond or is selected from the group consisting of C₁₋₈alkyl, C₁₋₈ alkenyl, C₁₋₈ alkynyl, C₇₋₁₂-alkylaryl, C₇₋₁₂-alkenylaryl,C₇₋₁₅-arylalkenyl, C₂₋₁₂-alkylheteroaryl, —CO—C₇₋₁₂ alkylaryl, —CO—C₇₋₁₂alkenylaryl, —CONR₆—C₁₋₈ alkyl, —NR₆CO—C₁₋₈ alkyl-, —NR₆—C₁₋₈ alkyl,—O—C₁₋₈ alkyl-, —CONR₆—C₅₋₆ aryl-, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₂₋₁₀heterocyclyl, —CO—C₂₋₁₀ heterocyclyl, —NR₆—CO—OC₁₋₈ alkyl, O—CO—NR₆—C₁₋₈alkyl, —NR₆CO—C₅₋₆ aryl-, —NR₆—C₅₋₆ aryl, —NR₆—C₁₋₆ heteroaryl, —C₁₋₈alkyl-O—C₅₋₆ aryl, —O—C₅₋₆ aryl, O—C₁₋₆ heteroaryl, —NR₆—CO—OC₅₋₆ aryl,—CONR₆—C₇₋₁₂ alkylaryl, —CONR₆—C₇₋₁₂ alkenylaryl, —SO₂—C₅₋₆ aryl,—SO₂—C₇₋₁₂ alkylaryl, —NR₆SO₂—C₇₋₁₂ alkylaryl, C₁₋₈ alkyl-CONR₆—C₅₋₆aryl, and O—CO—NR₆—C₅₋₆ aryl;R₆ is selected from the group consisting of hydrogen, C₁₋₈ alkyl, C₁₋₆haloalkyl, C₃₋₈ cycloalkyl, C₅₋₆ aryl, and C₁₋₆ heteroaryl, withheteroatoms selected from N, O, S;R₁ is selected from the group consisting of hydrogen, halogen hydroxy,nitro, cyano, azido, nitroso, oxo (═O), thioxo (═S), —SO₂—, amino,hydrazino, formyl, C₁₋₈ alkyl, C₁₋₈ haloalkyl, C₁₋₈ alkoxy, C₁₋₈haloalkoxy, C₇₋₁₂ arylalkoxy, C₃₋₈ cycloalkyl, C₃₋₈ cycloalkyloxy, C₂₋₁₀heterocyclyl, C₁₋₆ heteroaryl, alkylamino, —COOR_(a), —C(O)R_(b),—C(S)R_(a), —C(O)NR_(a)R_(b), —C(S)NR_(a)R_(b), —NR_(a)C(O)NR_(b)R_(c),NR_(a)C(S)NR_(b)R_(c), —N(R_(a))SOR_(b), —N(R_(a))SO₂R_(b),—NR_(a)C(O)OR_(b), —NR_(a)R_(b), —NR_(a)C(O)R_(b)—, —NR_(a)C(S)R_(b)—,—SONR_(a)R_(b)—, —SO₂NR_(a)R_(b)—, —OR_(a), —OR_(a)C(O)OR_(b)—,—OC(O)NR_(a)R_(b), OC(O)R_(a), —OC(O)NR_(a)R_(b)—, —R_(a)NR_(b)R_(c),—R_(a)OR_(b)—, —SR_(a), —SOR_(a) and —SO₂R_(a), wherein R_(a), R_(b) andR_(c) is independently selected from the group consisting of hydrogen,C₁₋₈ alkyl, C₃₋₈ cycloalkyl, C₅₋₆ aryl, C₇₋₁₅ arylalkyl, C₂₋₁₀heterocyclyl, C₁₋₆ heteroaryl, and C₂₋₁₂ heteroarylalkyl withheteroatoms selected from N, O, S;wherein C₇₋₁₂ arylalkoxy, C₁₋₈ alkyl, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₂₋₁₀heterocyclyl, C₃₋₈ cycloalkyl, is optionally substituted with one ormore of the groups selected from hydrogen, C₁₋₆ alkyl, C₅₋₆ aryl, C₁₋₆heteroaryl, C₂₋₁₀ heterocyclyl, oxo (═O), C₃₋₈ cycloalkyl, halogen, OH,amino, and cyano;R₃ is selected from the group consisting of hydrogen, substituted orunsubstituted C₁₋₈ alkyl, and C₅₋₆ aryl;R₂ is selected from the group consisting of —OR₇, aniline, amino C₅₋₆aryl, and amino C₁₋₆ heteroaryl,wherein aniline, amino C₅₋₆ aryl, and amino C₁₋₆ heteroaryl, isoptionally substituted with one or more of the groups selected from C₁₋₈alkyl, halogen, OH, amino, and cyano;R₇ is selected from the group consisting of hydrogen, C₁₋₈ alkyl, C₅₋₆aryl, C₂₋₁₀ heterocyclyl and —COR₈, wherein R₈ is selected from thegroup consisting of C₁₋₈ alkyl, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₃₋₈cycloalkyl, and C₂₋₁₀ heterocyclyl.

In an embodiment of the present invention, there is provided a compoundof

their analogs, tautomeric forms, stereoisomers, polymorphs, solvates,intermediates, pharmaceutically acceptable salts, metabolites, andprodrugs thereof;whereinAr is selected from the group consisting of substituted or unsubstitutedC₅₋₆ aryl, C₁₋₆ heteroaryl, and C₂₋₁₀ heterocyclyl with heteroatomsselected from N, O, S;W represents a bond or CR₄R₅, whereinR₄ and R₅ are independently selected from the group consisting ofhydrogen, substituted or unsubstituted C₁₋₈ alkyl, C₅₋₆ aryl, and C₁₋₆heteroaryl with heteroatoms selected from N, O, S;Y is a bond or is selected from the group consisting of substituted orunsubstituted C₁₋₈ alkyl, C₁₋₈ alkenyl, C₁₋₈ alkynyl, C₅₋₆ aryl, C₁₋₆heteroaryl, C₂₋₁₀ heterocyclyl, C₃₋₈ cycloalkyl, —CO—, and —CO—C₂₋₁₀heterocyclyl;wherein C₁₋₈ alkyl, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₂₋₁₀ heterocyclyl, C₃₋₈cycloalkyl, is optionally substituted with one or more of the groupsselected from hydrogen, C₁₋₆ alkyl, oxo (═O), C₃₋₈ cycloalkyl, halogen,OH, and cyano;Z represents a bond or is selected from the group consisting of C₁₋₈alkyl, C₁₋₈ alkenyl, C₁₋₈ alkynyl, C₇₋₁₂-alkylaryl, C₇₋₁₂-alkenylaryl,C₇₋₁₅-arylalkenyl, C₂₋₁₂-alkylheteroaryl, —CO—C₇₋₁₂ alkylaryl, —CO—C₇₋₁₂alkenylaryl, —CONR₆—C₁₋₈ alkyl, —NR₆CO—C₁₋₈ alkyl-, —NR₆—C₁₋₈ alkyl,—O—C₁₋₈ alkyl-, —CONR₆—C₅₋₆ aryl-, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₂₋₁₀heterocyclyl, —CO—C₂₋₁₀ heterocyclyl, —NR₆—CO—OC₁₋₈ alkyl, O—CO—NR₆—C₁₋₈alkyl, —NR₆CO—C₅₋₆ aryl-, —NR₆—C₅₋₆ aryl, —NR₆—C₁₋₆ heteroaryl, —C₁₋₈alkyl-O—C₅₋₆ aryl, —O—C₅₋₆ aryl, O—C₁₋₆ heteroaryl, —NR₆—CO—OC₅₋₆ aryl,—CONR₆—C₇₋₁₂ alkylaryl, —CONR₆—C₇₋₁₂ alkenylaryl, —SO₂—C₅₋₆ aryl,—SO₂—C₇₋₁₂ alkylaryl, —NR₆SO₂—C₇₋₁₂ alkylaryl, C₁₋₈ alkyl-CONR₆—C₅₋₆aryl, and O—CO—NR₆—C₅₋₆ aryl;R₆ is selected from the group consisting of hydrogen, C₁₋₈ alkyl, C₁₋₆haloalkyl, C₃₋₈ cycloalkyl, C₅₋₆ aryl, and C₁₋₆ heteroaryl, withheteroatoms selected from N, O, S;R₁ is selected from the group consisting of hydrogen, halogen hydroxy,nitro, cyano, azido, nitroso, oxo (═O), thioxo (═S), —SO₂—, amino,hydrazino, formyl, C₁₋₈ alkyl, C₁₋₈ haloalkyl, C₁₋₈ alkoxy, C₁₋₈haloalkoxy, C₇₋₁₂ arylalkoxy, C₃₋₈ cycloalkyl, C₃₋₈ cycloalkyloxy, C₅₋₆aryl, C₂₋₁₀ heterocyclyl, alkylamino, —COOR_(a), —C(O)R_(b), —C(S)R_(a),—C(O)NR_(a)R_(b), —C(S)NR_(a)R_(b), —NR_(a)C(O)NR_(b)R_(c),NR_(a)C(S)NR_(b)R_(c), —N(R_(a))SOR_(b), —N(R_(a))SO₂R_(b),—NR_(a)C(O)OR_(b), —NR_(a)R_(b), —NR_(a)C(O)R_(b)—, —NR_(a)C(S)R_(b)—,—SONR_(a)R_(b)—, —SO₂NR_(a)R_(b)—, —OR_(a), —OR_(a)C(O)OR_(b)—,—OC(O)NR_(a)R_(b), OC(O)R_(a), —OC(O)NR_(a)R_(b)—, —R_(a)NR_(b)R_(c),—R_(a)OR_(b)—, —SR_(a), —SOR_(a) and —SO₂R_(a), wherein R_(a), R_(b) andR_(c) is independently selected from the group consisting of hydrogen,C₁₋₈ alkyl, C₃₋₈ cycloalkyl, C₅₋₆ aryl, C₇₋₁₅ arylalkyl, C₂₋₁₀heterocyclyl, C₁₋₆ heteroaryl, and C₂₋₁₂ heteroarylalkyl withheteroatoms selected from N, O, S;wherein C₇₋₁₂ arylalkoxy, C₁₋₈ alkyl, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₂₋₁₀heterocyclyl, C₃₋₈ cycloalkyl, is optionally substituted with one ormore of the groups selected from hydrogen, C₁₋₆ alkyl, C₅₋₆ aryl, C₁₋₆heteroaryl, C₂₋₁₀ heterocyclyl, oxo (═O), C₃₋₈ cycloalkyl, halogen, OH,amino, and cyano;R₃ is selected from the group consisting of hydrogen, substituted orunsubstituted C₁₋₈ alkyl, and C₅₋₆ aryl;R₂ is selected from the group consisting of —OR₇, aniline, amino C₅₋₆aryl, and amino C₁₋₆ heteroaryl,wherein aniline, amino C₅₋₆ aryl, and amino C₁₋₆ heteroaryl, isoptionally substituted with one or more of the groups selected from C₁₋₈alkyl, halogen, OH, amino, and cyano;R₇ is selected from the group consisting of hydrogen, C₁₋₈ alkyl, C₅₋₆aryl, C₂₋₁₀ heterocyclyl and —COR₈, wherein R₈ is selected from thegroup consisting of C₁₋₈ alkyl, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₃₋₈cycloalkyl, and C₂₋₁₀ heterocyclyl.

In an embodiment of the present invention, there is provided a compoundof Formula I

their analogs, tautomeric forms, stereoisomers, polymorphs, solvates,intermediates, pharmaceutically acceptable salts, metabolites, andprodrugs thereof;whereinAr is selected from the group consisting of substituted or unsubstitutedC₅₋₆ aryl, C₁₋₆ heteroaryl, and C₂₋₁₀ heterocyclyl with heteroatomsselected from N, O, S;W represents a bond or CR₄R₅, whereinR₄ and R₅ are independently selected from the group consisting ofhydrogen, substituted or unsubstituted C₁₋₈ alkyl, C₅₋₆ aryl, and C₁₋₆heteroaryl with heteroatoms selected from N, O, S;Y is a bond or is selected from the group consisting of substituted orunsubstituted C₁₋₈ alkyl, C₁₋₈ alkenyl, C₁₋₈ alkynyl, C₅₋₆ aryl, C₁₋₆heteroaryl, C₂₋₁₀ heterocyclyl, C₃₋₈ cycloalkyl, —CO—, and —CO—C₂₋₁₀heterocyclyl;wherein C₁₋₈ alkyl, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₂₋₁₀ heterocyclyl, C₃₋₈cycloalkyl, is optionally substituted with one or more of the groupsselected from hydrogen, C₁₋₆ alkyl, oxo (═O), C₃₋₈ cycloalkyl, halogen,OH, and cyano;Z represents a bond or is selected from the group consisting of C₁₋₈alkyl, C₁₋₈ alkenyl, C₁₋₈ alkynyl, C₇₋₁₂-alkylaryl, C₇₋₁₂-alkenylaryl,C₇₋₁₅-arylalkenyl, C₂₋₁₂-alkylheteroaryl, —CO—C₇₋₁₂ alkylaryl, —CO—C₇₋₁₂alkenylaryl, —CONR₆—C₁₋₈ alkyl, —NR₆CO—C₁₋₈ alkyl-, —NR₆—C₁₋₈ alkyl,—O—C₁₋₈ alkyl-, —CONR₆—C₅₋₆ aryl-, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₂₋₁₀heterocyclyl, —CO—C₂₋₁₀ heterocyclyl, —NR₆—CO—OC₁₋₈ alkyl, O—CO—NR₆—C₁₋₈alkyl, —NR₆CO—C₅₋₆ aryl-, —NR₆—C₅₋₆ aryl, —NR₆—C₁₋₆ heteroaryl, —C₁₋₈alkyl-O—C₅₋₆ aryl, —O—C₅₋₆ aryl, O—C₁₋₆ heteroaryl, —NR₆—CO—OC₅₋₆ aryl,—CONR₆—C₇₋₁₂ alkylaryl, —CONR₆—C₇₋₁₂ alkenylaryl, —SO₂—C₅₋₆ aryl,—SO₂—C₇₋₁₂ alkylaryl, —NR₆SO₂—C₇₋₁₂ alkylaryl, C₁₋₈ alkyl-CONR₆—C₅₋₆aryl, and O—CO—NR₆—C₅₋₆ aryl;R₆ is selected from the group consisting of hydrogen, C₁₋₈ alkyl, C₁₋₆haloalkyl, C₃₋₈ cycloalkyl, C₅₋₆ aryl, and C₁₋₆ heteroaryl, withheteroatoms selected from N, O, S;R₁ is selected from the group consisting of hydrogen, halogen hydroxy,nitro, cyano, azido, nitroso, oxo (═O), thioxo (═S), —SO₂—, amino,hydrazino, formyl, C₁₋₈ alkyl, C₁₋₈ haloalkyl, C₁₋₈ haloalkoxy, C₇₋₁₂arylalkoxy, C₃₋₈ cycloalkyl, C₃₋₈ cycloalkyloxy, C₅₋₆ aryl, C₂₋₁₀heterocyclyl, C₁₋₆ heteroaryl, alkylamino, —COOR_(a), —C(O)R_(b),—C(S)R_(a), —C(O)NR_(a)R_(b), —C(S)NR_(a)R_(b), —NR_(a)C(O)NR_(b)R_(c),NR_(a)C(S)NR_(b)R_(c), —N(R_(a))SOR_(b), —N(R_(a))SO₂R_(b),—NR_(a)C(O)OR_(b), —NR_(a)R_(b), —NR_(a)C(O)R_(b)—, —NR_(a)C(S)R_(b)—,—SONR_(a)R_(b)—, —SO₂NR_(a)R_(b)—, —OR_(a), —OR_(a)C(O)OR_(b)—,—OC(O)NR_(a)R_(b), OC(O)R_(a), —OC(O)NR_(a)R_(b)—, —R_(a)NR_(b)R_(c),—R_(a)OR_(b)—, —SR_(a), —SOR_(a) and —SO₂R_(a), wherein R_(a), R_(b) andR_(c) is independently selected from the group consisting of hydrogen,C₁₋₈ alkyl, C₃₋₈ cycloalkyl, C₅₋₆ aryl, C₇₋₁₅ arylalkyl, C₂₋₁₀heterocyclyl, C₁₋₆ heteroaryl, and C₂₋₁₂ heteroarylalkyl withheteroatoms selected from N, O, S;wherein C₇₋₁₂ arylalkoxy, C₁₋₈ alkyl, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₂₋₁₀heterocyclyl, C₃₋₈ cycloalkyl, is optionally substituted with one ormore of the groups selected from hydrogen, C₁₋₆ alkyl, C₅₋₆ aryl, C₁₋₆heteroaryl, C₂₋₁₀ heterocyclyl, oxo (═O), C₃₋₈ cycloalkyl, halogen, OH,amino, and cyano;R₃ is selected from the group consisting of hydrogen, substituted orunsubstituted C₁₋₈ alkyl, and C₅₋₆ aryl;R₂ is selected from the group consisting of —OR₇, aniline, amino C₅₋₆aryl, and amino C₁₋₆ heteroaryl,wherein aniline, amino C₅₋₆ aryl, and amino C₁₋₆ heteroaryl, isoptionally substituted with one or more of the groups selected from C₁₋₈alkyl, halogen, OH, amino, and cyano;R₇ is selected from the group consisting of hydrogen, C₁₋₈ alkyl, C₅₋₆aryl, C₂₋₁₀ heterocyclyl and —COR₈, wherein R₈ is selected from thegroup consisting of C₁₋₈ alkyl, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₃₋₈cycloalkyl, and C₂₋₁₀ heterocyclyl.

In an embodiment of the present invention, there is provided a compoundof Formula I

their analogs, tautomeric forms, stereoisomers, polymorphs, solvates,intermediates, pharmaceutically acceptable salts, metabolites, andprodrugs thereof;whereinAr is selected from the group consisting of substituted or unsubstitutedC₅₋₆aryl, C₁₋₆ heteroaryl, and C₂₋₁₀ heterocyclyl with heteroatomsselected from N, O, S;W represents a bond or CR₄R₅, whereinR₄ and R₅ are independently selected from the group consisting ofhydrogen, substituted or unsubstituted C₁₋₈ alkyl, C₅₋₆ aryl, and C₁₋₆heteroaryl with heteroatoms selected from N, O, S;Y is a bond or is selected from the group consisting of substituted orunsubstituted C₁₋₈ alkyl, C₁₋₈ alkenyl, C₁₋₈ alkynyl, C₅₋₆ aryl, C₁₋₆heteroaryl, C₂₋₁₀ heterocyclyl, C₃₋₈ cycloalkyl, —CO—, and —CO—C₂₋₁₀heterocyclyl;wherein C₁₋₈ alkyl, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₂₋₁₀ heterocyclyl, C₃₋₈cycloalkyl, is optionally substituted with one or more of the groupsselected from hydrogen, C₁₋₆ alkyl, oxo (═O), C₃₋₈ cycloalkyl, halogen,OH, and cyano;Z represents a bond or is selected from the group consisting of C₁₋₈alkyl, C₁₋₈ alkenyl, C₁₋₈ alkynyl, C₇₋₁₂-alkylaryl, C₇₋₁₂-alkenylaryl,C₇₋₁₅-arylalkenyl, C₂₋₁₂-alkylheteroaryl, —CO—C₇₋₁₂ alkylaryl, —CO—C₇₋₁₂alkenylaryl, —CONR₆—C₁₋₈ alkyl, —NR₆CO—C₁₋₈ alkyl-, —NR₆—C₁₋₈ alkyl,—O—C₁₋₈ alkyl-, —CONR₆—C₅₋₆ aryl-, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₂₋₁₀heterocyclyl, —CO—C₂₋₁₀ heterocyclyl, —NR₆—CO—OC₁₋₈ alkyl, O—CO—NR₆—C₁₋₈alkyl, —NR₆CO—C₅₋₆ aryl-, —NR₆—C₅₋₆ aryl, —NR₆—C₁₋₆ heteroaryl, —C₁₋₈alkyl-O—C₅₋₆ aryl, —O—C₅₋₆ aryl, O—C₁₋₆ heteroaryl, —NR₆—CO—OC₅₋₆ aryl,—CONR₆—C₇₋₁₂ alkylaryl, —CONR₆—C₇₋₁₂ alkenylaryl, —SO₂—C₅₋₆ aryl,—SO₂—C₇₋₁₂ alkylaryl, —NR₆SO₂—C₇₋₁₂ alkylaryl, C₁₋₈ alkyl-CONR₆—C₅₋₆aryl, and O—CO—NR₆—C₅₋₆ aryl;R₆ is selected from the group consisting of hydrogen, C₁₋₈ alkyl, C₁₋₆haloalkyl, C₃₋₈ cycloalkyl, C₅₋₆ aryl, and C₁₋₆ heteroaryl, withheteroatoms selected from N, O, S;R₁ is selected from the group consisting of hydrogen, halogen hydroxy,nitro, cyano, azido, nitroso, oxo (═O), thioxo (═S), —SO₂—, amino,hydrazino, formyl, C₁₋₈ alkyl, C₁₋₈ haloalkyl, C₁₋₈ alkoxy, C₁₋₈haloalkoxy, C₃₋₈ cycloalkyl, C₃₋₈ cycloalkyloxy, C₅₋₆ aryl, C₂₋₁₀heterocyclyl, C₁₋₆ heteroaryl, alkylamino, —COOR_(a), —C(O)R_(b),—C(S)R_(a), —C(O)NR_(a)R_(b), —C(S)NR_(a)R_(b), —NR_(a)C(O)NR_(b)R_(c),NR_(a)C(S)NR_(b)R_(c), —N(R_(a))SOR_(b), —N(R_(a))SO₂R_(b),—NR_(a)C(O)OR_(b), —NR_(a)R_(b), —NR_(a)C(O)R_(b)—, —NR_(a)C(S)R_(b)—,—SONR_(a)R_(b)—, —SO₂NR_(a)R_(b)—, —OR_(a), —OR_(a)C(O)OR_(b)—,—OC(O)NR_(a)R_(b), OC(O)R_(a), —OC(O)NR_(a)R_(b)—, —R_(a)NR_(b)R_(c),—R_(a)OR_(b)—, —SR_(a), —SOR_(a) and —SO₂R_(a), wherein R_(a), R_(b) andR_(c) is independently selected from the group consisting of hydrogen,C₁₋₈ alkyl, C₃₋₈ cycloalkyl, C₅₋₆ aryl, C₇₋₁₅ arylalkyl, C₂₋₁₀heterocyclyl, C₁₋₆ heteroaryl, and C₂₋₁₂ heteroarylalkyl withheteroatoms selected from N, O, S;wherein C₇₋₁₂ arylalkoxy, C₁₋₈ alkyl, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₂₋₁₀heterocyclyl, C₃₋₈ cycloalkyl, is optionally substituted with one ormore of the groups selected from hydrogen, C₁₋₆ alkyl, C₅₋₆ aryl, C₁₋₆heteroaryl, C₂₋₁₀ heterocyclyl, oxo (═O), C₃₋₈ cycloalkyl, halogen, OH,amino, and cyano;R₃ is selected from the group consisting of hydrogen, substituted orunsubstituted C₁₋₈ alkyl, and C₅₋₆ aryl;R₂ is selected from the group consisting of —OR₇, aniline, amino C₅₋₆aryl, and amino C₁₋₆ heteroaryl,wherein aniline, amino C₅₋₆ aryl, and amino C₁₋₆ heteroaryl, isoptionally substituted with one or more of the groups selected from C₁₋₈alkyl, halogen, OH, amino, and cyano;R₇ is selected from the group consisting of hydrogen, C₁₋₈ alkyl, C₅₋₆aryl, C₂₋₁₀ heterocyclyl and —COR₈, wherein R₈ is selected from thegroup consisting of C₁₋₈ alkyl, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₃₋₈cycloalkyl, and C₂₋₁₀ heterocyclyl.

In an embodiment of the present invention, there is provided a compoundof Formula I

their analogs, tautomeric forms, stereoisomers, polymorphs, solvates,intermediates, pharmaceutically acceptable salts, metabolites, andprodrugs thereof;whereinAr is selected from the group consisting of substituted or unsubstitutedC₅₋₆aryl, C₁₋₆ heteroaryl, and C₂₋₁₀ heterocyclyl with heteroatomsselected from N, O, S;W represents a bond or CR₄R₅, whereinR₄ and R₅ are independently selected from the group consisting ofhydrogen, substituted or unsubstituted C₁₋₈ alkyl, C₅₋₆ aryl, and C₁₋₆heteroaryl with heteroatoms selected from N, O, S;Y is a bond or is selected from the group consisting of substituted orunsubstituted C₁₋₈ alkyl, C₁₋₈ alkenyl, C₁₋₈ alkynyl, C₅₋₆ aryl, C₁₋₆heteroaryl, C₂₋₁₀ heterocyclyl, C₃₋₈ cycloalkyl, —CO—, and —CO—C₂₋₁₀heterocyclyl;wherein C₁₋₈ alkyl, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₂₋₁₀ heterocyclyl, C₃₋₈cycloalkyl, is optionally substituted with one or more of the groupsselected from hydrogen, C₁₋₆ alkyl, oxo (═O), C₃₋₈ cycloalkyl, halogen,OH, and cyano;Z represents a bond or is selected from the group consisting of C₁₋₈alkyl, C₁₋₈ alkenyl, C₁₋₈ alkynyl, C₇₋₁₂-alkylaryl, C₇₋₁₂-alkenylaryl,C₇₋₁₅-arylalkenyl, C₂₋₁₂-alkylheteroaryl, —CO—C₇₋₁₂ alkylaryl, —CO—C₇₋₁₂alkenylaryl, —CONR₆—C₁₋₈ alkyl, —NR₆CO—C₁₋₈ alkyl-, —NR₆—C₁₋₈ alkyl,—O—C₁₋₈ alkyl-, —CONR₆—C₅₋₆ aryl-, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₂₋₁₀heterocyclyl, —CO—C₂₋₁₀ heterocyclyl, —NR₆—CO—OC₁₋₈ alkyl, O—CO—NR₆—C₁₋₈alkyl, —NR₆CO—C₅₋₆ aryl-, —NR₆—C₅₋₆ aryl, —NR₆—C₁₋₆ heteroaryl, —C₁₋₈alkyl-O—C₅₋₆ aryl, —O—C₅₋₆ aryl, O—C₁₋₆ heteroaryl, —NR₆—CO—OC₅₋₆ aryl,—CONR₆—C₇₋₁₂ alkylaryl, —CONR₆—C₇₋₁₂ alkenylaryl, —SO₂—C₅₋₆ aryl,—SO₂—C₇₋₁₂ alkylaryl, —NR₆SO₂—C₇₋₁₂ alkylaryl, C₁₋₈ alkyl-CONR₆—C₅₋₆aryl, and O—CO—NR₆—C₅₋₆ aryl;R₆ is selected from the group consisting of hydrogen, C₁₋₈ alkyl, C₁₋₆haloalkyl, C₃₋₈ cycloalkyl, C₅₋₆ aryl, and C₁₋₆ heteroaryl, withheteroatoms selected from N, O, S;R₁ is selected from the group consisting of hydrogen, hydroxy, nitro,cyano, azido, nitroso, oxo (═O), thioxo (═S), —SO₂—, amino, hydrazino,formyl, C₁₋₈ alkyl, C₁₋₈ haloalkyl, C₁₋₈ alkoxy, C₁₋₈ haloalkoxy, C₇₋₁₂arylalkoxy, C₃₋₈ cycloalkyl, C₃₋₈ cycloalkyloxy, C₅₋₆ aryl, C₂₋₁₀heterocyclyl, C₁₋₆ heteroaryl, alkylamino, —COOR_(a), —C(O)R_(b),—C(S)R_(a), —C(O)NR_(a)R_(b), —C(S)NR_(a)R_(b), —NR_(a)C(O)NR_(b)R_(c),NR_(a)C(S)NR_(b)R_(c), —N(R_(a))SOR_(b), —N(R_(a))SO₂R_(b),—NR_(a)C(O)OR_(b), —NR_(a)R_(b), —NR_(a)C(O)R_(b)—, —NR_(a)C(S)R_(b)—,—SONR_(a)R_(b)—, —SO₂NR_(a)R_(b)—, —OR_(a), —OR_(a)C(O)OR_(b)—,—OC(O)NR_(a)R_(b), OC(O)R_(a), —OC(O)NR_(a)R_(b)—, —R_(a)NR_(b)R_(c),—R_(a)OR_(b)—, —SR_(a), —SOR_(a) and —SO₂R_(a), wherein R_(a), R_(b) andR_(c) is independently selected from the group consisting of hydrogen,C₁₋₈ alkyl, C₃₋₈ cycloalkyl, C₅₋₆ aryl, C₇₋₁₅ arylalkyl, C₂₋₁₀heterocyclyl, C₁₋₆ heteroaryl, and C₂₋₁₂ heteroarylalkyl withheteroatoms selected from N, O, S;wherein C₇₋₁₂ arylalkoxy, C₁₋₈ alkyl, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₂₋₁₀heterocyclyl, C₃₋₈ cycloalkyl, is optionally substituted with one ormore of the groups selected from hydrogen, C₁₋₆ alkyl, C₅₋₆ aryl, C₁₋₆heteroaryl, C₂₋₁₀ heterocyclyl, oxo (═O), C₃₋₈ cycloalkyl, halogen, OH,amino, and cyano;R₃ is selected from the group consisting of hydrogen, substituted orunsubstituted C₁₋₈ alkyl, and C₅₋₆ aryl;R₂ is selected from the group consisting of —OR₇, aniline, amino C₅₋₆aryl, and amino C₁₋₆ heteroaryl,wherein aniline, amino C₅₋₆ aryl, and amino C₁₋₆ heteroaryl, isoptionally substituted with one or more of the groups selected from C₁₋₈alkyl, halogen, OH, amino, and cyano;R₇ is selected from the group consisting of hydrogen, C₁₋₈ alkyl, C₅₋₆aryl, C₂₋₁₀ heterocyclyl and —COR₈, wherein R₈ is selected from thegroup consisting of C₁₋₈ alkyl, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₃₋₈cycloalkyl, and C₂₋₁₀ heterocyclyl.

In an embodiment of the present invention, there is provided a compoundof Formula I

their analogs, tautomeric forms, stereoisomers, polymorphs, solvates,intermediates, pharmaceutically acceptable salts, metabolites, andprodrugs thereof;whereinAr is selected from the group consisting of substituted or unsubstitutedC₅₋₆aryl, C₁₋₆ heteroaryl, and C₂₋₁₀ heterocyclyl with heteroatomsselected from N, O, S;W represents a bond or CR₄R₅, whereinR₄ and R₅ are independently selected from the group consisting ofhydrogen, substituted or unsubstituted C₁₋₈ alkyl, C₅₋₆ aryl, and C₁₋₆heteroaryl with heteroatoms selected from N, O, S;Y is a bond or is selected from the group consisting of substituted orunsubstituted C₁₋₈ alkyl, C₁₋₈ alkenyl, C₁₋₈ alkynyl, C₅₋₆ aryl, C₁₋₆heteroaryl, C₂₋₁₀ heterocyclyl, C₃₋₈ cycloalkyl, —CO—, and —CO—C₂₋₁₀heterocyclyl;wherein C₁₋₈ alkyl, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₂₋₁₀ heterocyclyl, C₃₋₈cycloalkyl, is optionally substituted with one or more of the groupsselected from hydrogen, C₁₋₆ alkyl, oxo (═O), C₃₋₈ cycloalkyl, halogen,OH, and cyano;Z represents a bond or is selected from the group consisting of C₁₋₈alkyl, C₁₋₈ alkenyl, C₁₋₈ alkynyl, C₇₋₁₂-alkylaryl, C₇₋₁₂-alkenylaryl,C₇₋₁₅-arylalkenyl, C₂₋₁₂-alkylheteroaryl, —CO—C₇₋₁₂ alkylaryl, —CO—C₇₋₁₂alkenylaryl, —CONR₆—C₁₋₈ alkyl, —NR₆CO—C₁₋₈ alkyl-, —NR₆—C₁₋₈ alkyl,—O—C₁₋₈ alkyl-, —CONR₆—C₅₋₆ aryl-, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₂₋₁₀heterocyclyl, —CO—C₂₋₁₀ heterocyclyl, —NR₆—CO—OC₁₋₈ alkyl, O—CO—NR₆—C₁₋₈alkyl, —NR₆CO—C₅₋₆ aryl-, —NR₆—C₅₋₆ aryl, —NR₆—C₁₋₆ heteroaryl, —C₁₋₈alkyl-O—C₅₋₆ aryl, —O—C₅₋₆ aryl, O—C₁₋₆ heteroaryl, —NR₆—CO—OC₅₋₆ aryl,—CONR₆—C₇₋₁₂ alkylaryl, —CONR₆—C₇₋₁₂ alkenylaryl, —SO₂—C₅₋₆ aryl,—SO₂—C₇₋₁₂ alkylaryl, —NR₆SO₂—C₇₋₁₂ alkylaryl, C₁₋₈ alkyl-CONR₆—C₅₋₆aryl, and O—CO—NR₆—C₅₋₆ aryl;R₆ is selected from the group consisting of hydrogen, C₁₋₈ alkyl, C₁₋₆haloalkyl, C₃₋₈ cycloalkyl, C₅₋₆ aryl, and C₁₋₆ heteroaryl, withheteroatoms selected from N, O, S;R₁ is selected from the group consisting of halogen, hydroxy, nitro,cyano, azido, nitroso, oxo (═O), thioxo (═S), —SO₂—, amino, hydrazino,formyl, C₁₋₈ alkyl, C₁₋₈ haloalkyl, C₁₋₈ alkoxy, C₁₋₈ haloalkoxy, C₇₋₁₂arylalkoxy, C₃₋₈ cycloalkyl, C₃₋₈ cycloalkyloxy, C₅₋₆ aryl, C₂₋₁₀heterocyclyl, C₁₋₆ heteroaryl, alkylamino, —COOR_(a), —C(O)R_(b),—C(S)R_(a), —C(O)NR_(a)R_(b), —C(S)NR_(a)R_(b), —NR_(a)C(O)NR_(b)R_(c),NR_(a)C(S)NR_(b)R_(c), —N(R_(a))SOR_(b), —N(R_(a))SO₂R_(b),—NR_(a)C(O)OR_(b), —NR_(a)R_(b), —NR_(a)C(O)R_(b)—, —NR_(a)C(S)R_(b)—,—SONR_(a)R_(b)—, —SO₂NR_(a)R_(b)—, —OR_(a), —OR_(a)C(O)OR_(b)—,—OC(O)NR_(a)R_(b), OC(O)R_(a), —OC(O)NR_(a)R_(b)—, —R_(a)NR_(b)R_(c),—R_(a)OR_(b)—, —SR_(a), —SOR_(a) and —SO₂R_(a), wherein R_(a), R_(b) andR_(c) is independently selected from the group consisting of hydrogen,C₁₋₈ alkyl, C₃₋₈ cycloalkyl, C₅₋₆ aryl, C₇₋₁₅ arylalkyl, C₂₋₁₀heterocyclyl, C₁₋₆ heteroaryl, and C₂₋₁₂ heteroarylalkyl withheteroatoms selected from N, O, S;wherein C₇₋₁₂ arylalkoxy, C₁₋₈ alkyl, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₂₋₁₀heterocyclyl, C₃₋₈ cycloalkyl, is optionally substituted with one ormore of the groups selected from hydrogen, C₁₋₆ alkyl, C₅₋₆ aryl, C₁₋₆heteroaryl, C₂₋₁₀ heterocyclyl, oxo (═O), C₃₋₈ cycloalkyl, halogen, OH,amino, and cyano;R₃ is selected from the group consisting of hydrogen, substituted orunsubstituted C₁₋₈ alkyl, and C₅₋₆ aryl;R₂ is selected from the group consisting of —OR₇, aniline, amino C₅₋₆aryl, and amino C₁₋₆ heteroaryl,wherein aniline, amino C₅₋₆ aryl, and amino C₁₋₆ heteroaryl, isoptionally substituted with one or more of the groups selected from C₁₋₈alkyl, halogen, OH, amino, and cyano;R₇ is selected from the group consisting of hydrogen, C₁₋₈ alkyl, C₅₋₆aryl, C₂₋₁₀ heterocyclyl and —COR₈, wherein R₈ is selected from thegroup consisting of C₁₋₈ alkyl, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₃₋₈cycloalkyl, and C₂₋₁₀ heterocyclyl.

In an embodiment of the present invention, there is provided a compoundof Formula I

their analogs, tautomeric forms, stereoisomers, polymorphs, solvates,intermediates, pharmaceutically acceptable salts, metabolites, andprodrugs thereof;whereinAr is selected from the group consisting of substituted or unsubstitutedC₅₋₆ aryl, C₁₋₆ heteroaryl, and C₂₋₁₀ heterocyclyl with heteroatomsselected from N, O, S;W represents a bond or CR₄R₅, whereinR₄ and R₅ are independently selected from the group consisting ofhydrogen, substituted or unsubstituted C₁₋₈ alkyl, C₅₋₆ aryl, and C₁₋₆heteroaryl with heteroatoms selected from N, O, S;Y is a bond or is selected from the group consisting of substituted orunsubstituted C₁₋₈ alkyl, C₁₋₈ alkenyl, C₁₋₈ alkynyl, C₅₋₆ aryl, C₁₋₆heteroaryl, C₂₋₁₀ heterocyclyl, C₃₋₈ cycloalkyl, —CO—, and —CO—C₂₋₁₀heterocyclyl;wherein C₁₋₈ alkyl, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₂₋₁₀ heterocyclyl, C₃₋₈cycloalkyl, is optionally substituted with one or more of the groupsselected from hydrogen, C₁₋₆ alkyl, oxo (═O), C₃₋₈ cycloalkyl, halogen,OH, and cyano;Z represents a bond or is selected from the group consisting of C₁₋₈alkyl, C₁₋₈ alkenyl, C₁₋₈ alkynyl, C₇₋₁₂-alkylaryl, C₇₋₁₂-alkenylaryl,C₇₋₁₅-arylalkenyl, C₂₋₁₂-alkylheteroaryl, —CO—C₇₋₁₂ alkylaryl, —CO—C₇₋₁₂alkenylaryl, —CONR₆—C₁₋₈ alkyl, —NR₆CO—C₁₋₈ alkyl-, —NR₆—C₁₋₈ alkyl,—O—C₁₋₈ alkyl-, —CONR₆—C₅₋₆ aryl-, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₂₋₁₀heterocyclyl, —CO—C₂₋₁₀ heterocyclyl, —NR₆—CO—OC₁₋₈ alkyl, O—CO—NR₆—C₁₋₈alkyl, —NR₆CO—C₅₋₆ aryl-, —NR₆—C₅₋₆ aryl, —NR₆—C₁₋₆ heteroaryl, —C₁₋₈alkyl-O—C₅₋₆ aryl, —O—C₅₋₆ aryl, O—C₁₋₆ heteroaryl, —NR₆—CO—OC₅₋₆ aryl,—CONR₆—C₇₋₁₂ alkylaryl, —CONR₆—C₇₋₁₂ alkenylaryl, —SO₂—C₅₋₆ aryl,—SO₂—C₇₋₁₂ alkylaryl, —NR₆SO₂—C₇₋₁₂ alkylaryl, C₁₋₈ alkyl-CONR₆—C₅₋₆aryl, and O—CO—NR₆—C₅₋₆ aryl;R₆ is selected from the group consisting of hydrogen, C₁₋₈ alkyl, C₁₋₆haloalkyl, C₃₋₈ cycloalkyl, C₅₋₆ aryl, and C₁₋₆ heteroaryl, withheteroatoms selected from N, O, S;R₁ is selected from the group consisting of hydrogen, halogen, hydroxy,nitro, cyano, azido, nitroso, oxo (═O), thioxo (═S), —SO₂—, amino,hydrazino, formyl, C₁₋₈ alkyl, C₁₋₈ haloalkyl, C₁₋₈ alkoxy, C₁₋₈haloalkoxy, C₇₋₁₂ arylalkoxy, C₃₋₈ cycloalkyl, C₃₋₈ cycloalkyloxy, C₅₋₆aryl, C₂₋₁₀ heterocyclyl, C₁₋₆ heteroaryl, alkylamino, —COOR_(a),—C(S)R_(a), —C(O)NR_(a)R_(b), —C(S)NR_(a)R_(b), —NR_(a)C(O)NR_(b)R_(c),NR_(a)C(S)NR_(b)R_(c), —N(R_(a))SOR_(b), —N(R_(a))SO₂R_(b),—NR_(a)C(O)OR_(b), —NR_(a)R_(b), —NR_(a)C(O)R_(b)—, —NR_(a)C(S)R_(b)—,—SONR_(a)R_(b)—, —SO₂NR_(a)R_(b)—, —OR_(a), —OR_(a)C(O)OR_(b)—,—OC(O)NR_(a)R_(b), OC(O)R_(a), —OC(O)NR_(a)R_(b)—, —R_(a)NR_(b)R_(c),—R_(a)OR_(b)—, —SR_(a), —SOR_(a) and —SO₂R_(a), wherein R_(a), R_(b) andR_(c) is independently selected from the group consisting of hydrogen,C₁₋₈ alkyl, C₃₋₈ cycloalkyl, C₅₋₆ aryl, C₇₋₁₅ arylalkyl, C₂₋₁₀heterocyclyl, C₁₋₆ heteroaryl, and C₂₋₁₂ heteroarylalkyl withheteroatoms selected from N, O, S;wherein C₇₋₁₂ arylalkoxy, C₁₋₈ alkyl, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₂₋₁₀heterocyclyl, C₃₋₈ cycloalkyl, is optionally substituted with one ormore of the groups selected from hydrogen, C₁₋₆ alkyl, C₅₋₆ aryl, C₁₋₆heteroaryl, C₂₋₁₀ heterocyclyl, oxo (═O), C₃₋₈ cycloalkyl, halogen, OH,amino, and cyano;R₃ is selected from the group consisting of hydrogen, substituted orunsubstituted C₁₋₈ alkyl, and C₅₋₆ aryl;R₂ is selected from the group consisting of —OR₇, aniline, amino C₅₋₆aryl, and amino C₁₋₆ heteroaryl,wherein aniline, amino C₅₋₆ aryl, and amino C₁₋₆ heteroaryl, isoptionally substituted with one or more of the groups selected from C₁₋₈alkyl, halogen, OH, amino, and cyano;R₇ is selected from the group consisting of hydrogen, C₁₋₈ alkyl, C₅₋₆aryl, C₂₋₁₀ heterocyclyl and —COR₈, wherein R₈ is selected from thegroup consisting of C₁₋₈ alkyl, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₃₋₈cycloalkyl, and C₂₋₁₀ heterocyclyl.

In an embodiment of the present invention, there is provided a compoundof Formula I

their analogs, tautomeric forms, stereoisomers, polymorphs, solvates,intermediates, pharmaceutically acceptable salts, metabolites, andprodrugs thereof;whereinAr is selected from the group consisting of substituted or unsubstitutedC₅₋₆ aryl, C₁₋₆ heteroaryl, and C₂₋₁₀ heterocyclyl with heteroatomsselected from N, O, S;W represents a bond or CR₄R₅, whereinR₄ and R₅ are independently selected from the group consisting ofhydrogen, substituted or unsubstituted C₁₋₈ alkyl, C₅₋₆ aryl, and C₁₋₆heteroaryl with heteroatoms selected from N, O, S;Y is a bond or is selected from the group consisting of substituted orunsubstituted C₁₋₈ alkyl, C₁₋₈ alkenyl, C₁₋₈ alkynyl, C₅₋₆ aryl, C₁₋₆heteroaryl, C₂₋₁₀ heterocyclyl, C₃₋₈ cycloalkyl, —CO—, and —CO—C₂₋₁₀heterocyclyl;wherein C₁₋₈ alkyl, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₂₋₁₀ heterocyclyl, C₃₋₈cycloalkyl, is optionally substituted with one or more of the groupsselected from hydrogen, C₁₋₆ alkyl, oxo (═O), C₃₋₈ cycloalkyl, halogen,OH, and cyano;Z represents a bond or is selected from the group consisting of C₁₋₈alkyl, C₁₋₈ alkenyl, C₁₋₈ alkynyl, C₇₋₁₂-alkylaryl, C₇₋₁₂-alkenylaryl,C₇₋₁₅-arylalkenyl, C₂₋₁₂-alkylheteroaryl, —CO—C₇₋₁₂ alkylaryl, —CO—C₇₋₁₂alkenylaryl, —CONR₆—C₁₋₈ alkyl, —NR₆CO—C₁₋₈ alkyl-, —NR₆—C₁₋₈ alkyl,—O—C₁₋₈ alkyl-, —CONR₆—C₅₋₆ aryl-, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₂₋₁₀heterocyclyl, —CO—C₂₋₁₀ heterocyclyl, —NR₆—CO—OC₁₋₈ alkyl, O—CO—NR₆—C₁₋₈alkyl, —NR₆CO—C₅₋₆ aryl-, —NR₆—C₅₋₆ aryl, —NR₆—C₁₋₆ heteroaryl, —C₁₋₈alkyl-O—C₅₋₆ aryl, —O—C₅₋₆ aryl, O—C₁₋₆ heteroaryl, —NR₆—CO—OC₅₋₆ aryl,—CONR₆—C₇₋₁₂ alkylaryl, —CONR₆—C₇₋₁₂ alkenylaryl, —SO₂—C₅₋₆ aryl,—SO₂—C₇₋₁₂ alkylaryl, —NR₆SO₂—C₇₋₁₂ alkylaryl, C₁₋₈ alkyl-CONR₆—C₅₋₆aryl, and O—CO—NR₆—C₅₋₆ aryl;R₆ is selected from the group consisting of hydrogen, C₁₋₈ alkyl, C₁₋₆haloalkyl, C₃₋₈ cycloalkyl, C₅₋₆ aryl, and C₁₋₆ heteroaryl, withheteroatoms selected from N, O, S;R₁ is selected from the group consisting of hydrogen, halogen, hydroxy,nitro, cyano, azido, nitroso, oxo (═O), thioxo (═S), —SO₂—, amino,hydrazino, formyl, C₁₋₈ alkyl, C₁₋₈ haloalkyl, C₁₋₈ alkoxy, C₁₋₈haloalkoxy, C₇₋₁₂ arylalkoxy, C₃₋₈ cycloalkyl, C₃₋₈ cycloalkyloxy, C₅₋₆aryl, C₂₋₁₀ heterocyclyl, C₁₋₆ heteroaryl, alkylamino, —COOR_(a),—C(O)R_(b), —C(S)R_(a), —C(S)NR_(a)R_(b), —NR_(a)C(O)NR_(b)R_(c),NR_(a)C(S)NR_(b)R_(c), —N(R_(a))SOR_(b), —N(R_(a))SO₂R_(b),—NR_(a)C(O)OR_(b), —NR_(a)R_(b), —NR_(a)C(O)R_(b)—, —NR_(a)C(S)R_(b)—,—SONR_(a)R_(b)—, —SO₂NR_(a)R_(b)—, —OR_(a), —OR_(a)C(O)OR_(b)—,—OC(O)NR_(a)R_(b), OC(O)R_(a), —OC(O)NR_(a)R_(b)—, —R_(a)NR_(b)R_(c),—R_(a)OR_(b)—, —SR_(a), —SOR_(a) and —SO₂R_(a), wherein R_(a), R_(b) andR_(c) is independently selected from the group consisting of hydrogen,C₁₋₈ alkyl, C₃₋₈ cycloalkyl, C₅₋₆ aryl, C₇₋₁₅ arylalkyl, C₂₋₁₀heterocyclyl, C₁₋₆ heteroaryl, and C₂₋₁₂ heteroarylalkyl withheteroatoms selected from N, O, S;wherein C₇₋₁₂ arylalkoxy, C₁₋₈ alkyl, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₂₋₁₀heterocyclyl, C₃₋₈ cycloalkyl, is optionally substituted with one ormore of the groups selected from hydrogen, C₁₋₆ alkyl, C₅₋₆ aryl, C₁₋₆heteroaryl, C₂₋₁₀ heterocyclyl, oxo (═O), C₃₋₈ cycloalkyl, halogen, OH,amino, and cyano;R₃ is selected from the group consisting of hydrogen, substituted orunsubstituted C₁₋₈ alkyl, and C₅₋₆ aryl;R₂ is selected from the group consisting of —OR₇, aniline, amino C₅₋₆aryl, and amino C₁₋₆ heteroaryl,wherein aniline, amino C₅₋₆ aryl, and amino C₁₋₆ heteroaryl, isoptionally substituted with one or more of the groups selected from C₁₋₈alkyl, halogen, OH, amino, and cyano;R₇ is selected from the group consisting of hydrogen, C₁₋₈ alkyl, C₅₋₆aryl, C₂₋₁₀ heterocyclyl and —COR₈, wherein R₈ is selected from thegroup consisting of C₁₋₈ alkyl, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₃₋₈cycloalkyl, and C₂₋₁₀ heterocyclyl.

In an embodiment of the present invention, there is provided a compoundof Formula I

their analogs, tautomeric forms, stereoisomers, polymorphs, solvates,intermediates, pharmaceutically acceptable salts, metabolites, andprodrugs thereof;whereinAr is selected from the group consisting of substituted or unsubstitutedC₅₋₆ aryl, C₁₋₆ heteroaryl, and C₂₋₁₀ heterocyclyl with heteroatomsselected from N, O, S;W represents a bond or CR₄R₅, whereinR₄ and R₅ are independently selected from the group consisting ofhydrogen, substituted or unsubstituted C₁₋₈ alkyl, C₅₋₆ aryl, and C₁₋₆heteroaryl with heteroatoms selected from N, O, S;Y is a bond or is selected from the group consisting of substituted orunsubstituted C₁₋₈ alkyl, C₁₋₈ alkenyl, C₁₋₈ alkynyl, C₅₋₆ aryl, C₁₋₆heteroaryl, C₂₋₁₀ heterocyclyl, C₃₋₈ cycloalkyl, —CO—, and —CO—C₂₋₁₀heterocyclyl;wherein C₁₋₈ alkyl, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₂₋₁₀ heterocyclyl, C₃₋₈cycloalkyl, is optionally substituted with one or more of the groupsselected from hydrogen, C₁₋₆ alkyl, oxo (═O), C₃₋₈ cycloalkyl, halogen,OH, and cyano;Z represents a bond or is selected from the group consisting of C₁₋₈alkyl, C₁₋₈ alkenyl, C₁₋₈ alkynyl, C₇₋₁₂-alkylaryl, C₇₋₁₂-alkenylaryl,C₇₋₁₅-arylalkenyl, C₂₋₁₂-alkylheteroaryl, —CO—C₇₋₁₂ alkylaryl, —CO—C₇₋₁₂alkenylaryl, —CONR₆—C₁₋₈ alkyl, —NR₆CO—C₁₋₈ alkyl-, —NR₆—C₁₋₈ alkyl,—O—C₁₋₈ alkyl-, —CONR₆—C₅₋₆ aryl-, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₂₋₁₀heterocyclyl, —CO—C₂₋₁₀ heterocyclyl, —NR₆—CO—OC₁₋₈ alkyl, O—CO—NR₆—C₁₋₈alkyl, —NR₆CO—C₅₋₆ aryl-, —NR₆—C₅₋₆ aryl, —NR₆—C₁₋₆ heteroaryl, —C₁₋₈alkyl-O—C₅₋₆ aryl, —O—C₅₋₆ aryl, O—C₁₋₆ heteroaryl, —NR₆—CO—OC₅₋₆ aryl,—CONR₆—C₇₋₁₂ alkylaryl, —CONR₆—C₇₋₁₂ alkenylaryl, —SO₂—C₅₋₆ aryl,—SO₂—C₇₋₁₂ alkylaryl, —NR₆SO₂—C₇₋₁₂ alkylaryl, C₁₋₈ alkyl-CONR₆—C₅₋₆aryl, and O—CO—NR₆—C₅₋₆ aryl;R₆ is selected from the group consisting of hydrogen, C₁₋₈ alkyl, C₁₋₆haloalkyl, C₃₋₈ cycloalkyl, C₅₋₆ aryl, and C₁₋₆ heteroaryl, withheteroatoms selected from N, O, S;R₁ is selected from the group consisting of hydrogen, halogen, hydroxy,nitro, cyano, azido, nitroso, oxo (═O), thioxo (═S), —SO₂—, amino,hydrazino, formyl, C₁₋₈ haloalkyl, C₁₋₈ alkoxy, C₁₋₈ haloalkoxy, C₇₋₁₂arylalkoxy, C₃₋₈ cycloalkyl, C₃₋₈ cycloalkyloxy, C₅₋₆ aryl, C₂₋₁₀heterocyclyl, C₁₋₆ heteroaryl, alkylamino, —COOR_(a), —C(O)R_(b),—C(S)R_(a), —C(O)NR_(a)R_(b), —C(S)NR_(a)R_(b), —NR_(a)C(O)NR_(b)R_(c),NR_(a)C(S)NR_(b)R_(c), —N(R_(a))SOR_(b), —N(R_(a))SO₂R_(b),—NR_(a)C(O)OR_(b), —NR_(a)R_(b), —NR_(a)C(O)R_(b)—, —NR_(a)C(S)R_(b)—,—SONR_(a)R_(b)—, —SO₂NR_(a)R_(b)—, —OR_(a), —OR_(a)C(O)OR_(b)—,—OC(O)NR_(a)R_(b), OC(O)R_(a), —OC(O)NR_(a)R_(b)—, —R_(a)NR_(b)R_(c),—R_(a)OR_(b)—, —SR_(a), —SOR_(a) and —SO₂R_(a), wherein R_(a), R_(b) andR_(c) is independently selected from the group consisting of hydrogen,C₁₋₈ alkyl, C₃₋₈ cycloalkyl, C₅₋₆ aryl, C₇₋₁₅ arylalkyl, C₂₋₁₀heterocyclyl, C₁₋₆ heteroaryl, and C₂₋₁₂ heteroarylalkyl withheteroatoms selected from N, O, S;wherein C₇₋₁₂ arylalkoxy, C₁₋₈ alkyl, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₂₋₁₀heterocyclyl, C₃₋₈ cycloalkyl, is optionally substituted with one ormore of the groups selected from hydrogen, C₁₋₆ alkyl, C₅₋₆ aryl, C₁₋₆heteroaryl, C₂₋₁₀ heterocyclyl, oxo (═O), C₃₋₈ cycloalkyl, halogen, OH,amino, and cyano;R₃ is selected from the group consisting of hydrogen, substituted orunsubstituted C₁₋₈ alkyl, and C₅₋₆ aryl;R₂ is selected from the group consisting of —OR₇, aniline, amino C₅₋₆aryl, and amino C₁₋₆ heteroaryl,wherein aniline, amino C₅₋₆ aryl, and amino C₁₋₆ heteroaryl, isoptionally substituted with one or more of the groups selected from C₁₋₈alkyl, halogen, OH, amino, and cyano;R₇ is selected from the group consisting of hydrogen, C₁₋₈ alkyl, C₅₋₆aryl, C₂₋₁₀ heterocyclyl and —COR₈, wherein R₈ is selected from thegroup consisting of C₁₋₈ alkyl, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₃₋₈cycloalkyl, and C₂₋₁₀ heterocyclyl.

In an embodiment of the present invention, there is provided a compoundof Formula I

their analogs, tautomeric forms, stereoisomers, polymorphs, solvates,intermediates, pharmaceutically acceptable salts, metabolites, andprodrugs thereof;whereinAr is selected from the group consisting of substituted or unsubstitutedC₁₋₆ heteroaryl, and C₂₋₁₀ heterocyclyl with heteroatoms selected fromN, O, S;W represents a bond or CR₄R₅, whereinR₄ and R₅ are independently selected from the group consisting ofhydrogen, substituted or unsubstituted C₁₋₈ alkyl, C₅₋₆ aryl, and C₁₋₆heteroaryl with heteroatoms selected from N, O, S;Y is a bond or is selected from the group consisting of substituted orunsubstituted C₁₋₈ alkyl, C₁₋₈ alkenyl, C₁₋₈ alkynyl, C₅₋₆ aryl, C₁₋₆heteroaryl, C₂₋₁₀ heterocyclyl, C₃₋₈ cycloalkyl, —CO—, and —CO—C₂₋₁₀heterocyclyl;wherein C₁₋₈ alkyl, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₂₋₁₀ heterocyclyl, C₃₋₈cycloalkyl, is optionally substituted with one or more of the groupsselected from hydrogen, C₁₋₆ alkyl, oxo (═O), C₃₋₈ cycloalkyl, halogen,OH, and cyano;Z represents a bond or is selected from the group consisting of C₁₋₈alkyl, C₁₋₈ alkenyl, C₁₋₈ alkynyl, C₇₋₁₂-alkylaryl, C₇₋₁₂-alkenylaryl,C₇₋₁₅-arylalkenyl, C₂₋₁₂-alkylheteroaryl, —CO—C₇₋₁₂ alkylaryl, —CO—C₇₋₁₂alkenylaryl, —CONR₆—C₁₋₈ alkyl, —NR₆CO—C₁₋₈ alkyl-, —NR₆—C₁₋₈ alkyl,—O—C₁₋₈ alkyl-, —CONR₆—C₅₋₆ aryl-, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₂₋₁₀heterocyclyl, —CO—C₂₋₁₀ heterocyclyl, —NR₆—CO—OC₁₋₈ alkyl, O—CO—NR₆—C₁₋₈alkyl, —NR₆CO—C₅₋₆ aryl-, —NR₆—C₅₋₆ aryl, —NR₆—C₁₋₆ heteroaryl, —C₁₋₈alkyl-O—C₅₋₆ aryl, —O—C₅₋₆ aryl, O—C₁₋₆ heteroaryl, —NR₆—CO—OC₅₋₆ aryl,—CONR₆—C₇₋₁₂ alkylaryl, —CONR₆—C₇₋₁₂ alkenylaryl, —SO₂—C₅₋₆ aryl,—SO₂—C₇₋₁₂ alkylaryl, —NR₆SO₂—C₇₋₁₂ alkylaryl, C₁₋₈ alkyl-CONR₆—C₅₋₆aryl, and O—CO—NR₆—C₅₋₆ aryl;R₆ is selected from the group consisting of hydrogen, C₁₋₈ alkyl, C₁₋₆haloalkyl, C₃₋₈ cycloalkyl, C₅₋₆ aryl, and C₁₋₆ heteroaryl, withheteroatoms selected from N, O, S;R₁ is selected from the group consisting of hydrogen, halogen hydroxy,nitro, cyano, azido, nitroso, oxo (═O), thioxo (═S), —SO₂—, amino,hydrazino, formyl, C₁₋₈ alkyl, C₁₋₈ haloalkyl, C₁₋₈ alkoxy, C₁₋₈haloalkoxy, C₇₋₁₂ arylalkoxy, C₃₋₈ cycloalkyl, C₃₋₈ cycloalkyloxy, C₅₋₆aryl, C₂₋₁₀ heterocyclyl, C₁₋₆ heteroaryl, alkylamino, —COOR_(a),—C(O)R_(b), —C(S)R_(a), —C(O)NR_(a)R_(b), —C(S)NR_(a)R_(b),—NR_(a)C(O)NR_(b)R_(c), NR_(a)C(S)NR_(b)R_(c), —N(R_(a))SOR_(b),—N(R_(a))SO₂R_(b), —NR_(a)C(O)OR_(b), —NR_(a)R_(b), —NR_(a)C(O)R_(b)—,—NR_(a)C(S)R_(b)—, —SONR_(a)R_(b)—, —SO₂NR_(a)R_(b)—, —OR_(a),—OR_(a)C(O)OR_(b)—, —OC(O)NR_(a)R_(b), OC(O)R_(a), —OC(O)NR_(a)R_(b)—,—R_(a)NR_(b)R_(c), —R_(a)OR_(b)—, —SR_(a), —SOR_(a) and —SO₂R_(a),wherein R_(a), R_(b) and R_(c) is independently selected from the groupconsisting of hydrogen, C₁₋₈ alkyl, C₃₋₈ cycloalkyl, C₅₋₆ aryl, C₇₋₁₅arylalkyl, C₂₋₁₀ heterocyclyl, C₁₋₆ heteroaryl, and C₂₋₁₂heteroarylalkyl with heteroatoms selected from N, O, S;wherein C₇₋₁₂ arylalkoxy, C₁₋₈ alkyl, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₂₋₁₀heterocyclyl, C₃₋₈ cycloalkyl, is optionally substituted with one ormore of the groups selected from hydrogen, C₁₋₆ alkyl, C₅₋₆ aryl, C₁₋₆heteroaryl, C₂₋₁₀ heterocyclyl, oxo (═O), C₃₋₈ cycloalkyl, halogen, OH,amino, and cyano;R₃ is selected from the group consisting of hydrogen, substituted orunsubstituted C₁₋₈ alkyl, and C₅₋₆ aryl;R₂ is selected from the group consisting of —OR₇, aniline, amino C₅₋₆aryl, and amino C₁₋₆ heteroaryl,wherein aniline, amino C₅₋₆ aryl, and amino C₁₋₆ heteroaryl, isoptionally substituted with one or more of the groups selected from C₁₋₈alkyl, halogen, OH, amino, and cyano;R₇ is selected from the group consisting of hydrogen, C₁₋₈ alkyl, C₅₋₆aryl, C₂₋₁₀ heterocyclyl and —COR₈, wherein R₈ is selected from thegroup consisting of C₁₋₈ alkyl, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₃₋₈cycloalkyl, and C₂₋₁₀ heterocyclyl.

In an embodiment of the present invention, there is provided a compoundof Formula I

their analogs, tautomeric forms, stereoisomers, polymorphs, solvates,intermediates, pharmaceutically acceptable salts, metabolites, andprodrugs thereof;whereinAr is selected from the group consisting of substituted or unsubstitutedC₅₋₆ aryl, and C₂₋₁₀ heterocyclyl with heteroatoms selected from N, O,S;W represents a bond or CR₄R₅, whereinR₄ and R₅ are independently selected from the group consisting ofhydrogen, substituted or unsubstituted C₁₋₈ alkyl, C₅₋₆ aryl, and C₁₋₆heteroaryl with heteroatoms selected from N, O, S;Y is a bond or is selected from the group consisting of substituted orunsubstituted C₁₋₈ alkyl, C₁₋₈ alkenyl, C₁₋₈ alkynyl, C₅₋₆ aryl, C₁₋₆heteroaryl, C₂₋₁₀ heterocyclyl, C₃₋₈ cycloalkyl, —CO—, and —CO—C₂₋₁₀heterocyclyl;wherein C₁₋₈ alkyl, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₂₋₁₀ heterocyclyl, C₃₋₈cycloalkyl, is optionally substituted with one or more of the groupsselected from hydrogen, C₁₋₆ alkyl, oxo (═O), C₃₋₈ cycloalkyl, halogen,OH, and cyano;Z represents a bond or is selected from the group consisting of C₁₋₈alkyl, C₁₋₈ alkenyl, C₁₋₈ alkynyl, C₇₋₁₂-alkylaryl, C₇₋₁₂-alkenylaryl,C₇₋₁₅-arylalkenyl, C₂₋₁₂-alkylheteroaryl, —CO—C₇₋₁₂ alkylaryl, —CO—C₇₋₁₂alkenylaryl, —CONR₆—C₁₋₈ alkyl, —NR₆CO—C₁₋₈ alkyl-, —NR₆—C₁₋₈ alkyl,—O—C₁₋₈ alkyl-, —CONR₆—C₅₋₆ aryl-, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₂₋₁₀heterocyclyl, —CO—C₂₋₁₀ heterocyclyl, —NR₆—CO—OC₁₋₈ alkyl, O—CO—NR₆—C₁₋₈alkyl, —NR₆CO—C₅₋₆ aryl-, —NR₆—C₅₋₆ aryl, —NR₆—C₁₋₆ heteroaryl, —C₁₋₈alkyl-O—C₅₋₆ aryl, —O—C₅₋₆ aryl, O—C₁₋₆ heteroaryl, —NR₆—CO—OC₅₋₆ aryl,—CONR₆—C₇₋₁₂ alkylaryl, —CONR₆—C₇₋₁₂ alkenylaryl, —SO₂—C₅₋₆ aryl,—SO₂—C₇₋₁₂ alkylaryl, —NR₆SO₂—C₇₋₁₂ alkylaryl, C₁₋₈ alkyl-CONR₆—C₅₋₆aryl, and O—CO—NR₆—C₅₋₆ aryl;R₆ is selected from the group consisting of hydrogen, C₁₋₈ alkyl, C₁₋₆haloalkyl, C₃₋₈ cycloalkyl, C₅₋₆ aryl, and C₁₋₆ heteroaryl, withheteroatoms selected from N, O, S;R₁ is selected from the group consisting of hydrogen, halogen, hydroxy,nitro, cyano, azido, nitroso, oxo (═O), thioxo (═S), —SO₂—, amino,hydrazino, formyl, C₁₋₈ alkyl, C₁₋₈ haloalkyl, C₁₋₈ alkoxy, C₁₋₈haloalkoxy, C₇₋₁₂ arylalkoxy, C₃₋₈ cycloalkyl, C₃₋₈ cycloalkyloxy, C₅₋₆aryl, C₂₋₁₀ heterocyclyl, C₁₋₆ heteroaryl, alkylamino, —COOR_(a),—C(O)R_(b), —C(S)R_(a), —C(O)NR_(a)R_(b), —C(S)NR_(a)R_(b),—NR_(a)C(O)NR_(b)R_(c), NR_(a)C(S)NR_(b)R_(c), —N(R_(a))SOR_(b),—N(R_(a))SO₂R_(b), —NR_(a)C(O)OR_(b), —NR_(a)R_(b), —NR_(a)C(O)R_(b)—,—NR_(a)C(S)R_(b)—, —SONR_(a)R_(b)—, —SO₂NR_(a)R_(b)—, —OR_(a),—OR_(a)C(O)OR_(b)—, —OC(O)NR_(a)R_(b), OC(O)R_(a), —OC(O)NR_(a)R_(b)—,—R_(a)NR_(b)R_(c), —R_(a)OR_(b)—, —SR_(a), —SOR_(a) and —SO₂R_(a),wherein R_(a), R_(b) and R_(c) is independently selected from the groupconsisting of hydrogen, C₁₋₈ alkyl, C₃₋₈ cycloalkyl, C₅₋₆ aryl, C₇₋₁₅arylalkyl, C₂₋₁₀ heterocyclyl, C₁₋₆ heteroaryl, and C₂₋₁₂heteroarylalkyl with heteroatoms selected from N, O, S;wherein C₇₋₁₂ arylalkoxy, C₁₋₈ alkyl, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₂₋₁₀heterocyclyl, C₃₋₈ cycloalkyl, is optionally substituted with one ormore of the groups selected from hydrogen, C₁₋₆ alkyl, C₅₋₆ aryl, C₁₋₆heteroaryl, C₂₋₁₀ heterocyclyl, oxo (═O), C₃₋₈ cycloalkyl, halogen, OH,amino, and cyano;R₃ is selected from the group consisting of hydrogen, substituted orunsubstituted C₁₋₈ alkyl, and C₅₋₆ aryl;R₂ is selected from the group consisting of —OR₇, aniline, amino C₅₋₆aryl, and amino C₁₋₆ heteroaryl,wherein aniline, amino C₅₋₆ aryl, and amino C₁₋₆ heteroaryl, isoptionally substituted with one or more of the groups selected from C₁₋₈alkyl, halogen, OH, amino, and cyano;R₇ is selected from the group consisting of hydrogen, C₁₋₈ alkyl, C₅₋₆aryl, C₂₋₁₀ heterocyclyl and —COR₈, wherein R₈ is selected from thegroup consisting of C₁₋₈ alkyl, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₃₋₈cycloalkyl, and C₂₋₁₀ heterocyclyl.

In an embodiment of the present invention, there is provided a compoundof Formula I

their analogs, tautomeric forms, stereoisomers, polymorphs, solvates,intermediates, pharmaceutically acceptable salts, metabolites, andprodrugs thereof;whereinAr is selected from the group consisting of substituted or unsubstitutedC₅₋₆ aryl, and C₁₋₆ heteroaryl with heteroatoms selected from N, O, S;W represents a bond or CR₄R₅, whereinR₄ and R₅ are independently selected from the group consisting ofhydrogen, substituted or unsubstituted C₁₋₈ alkyl, C₅₋₆ aryl, and C₁₋₆heteroaryl with heteroatoms selected from N, O, S;Y is a bond or is selected from the group consisting of substituted orunsubstituted C₁₋₈ alkyl, C₁₋₈ alkenyl, C₁₋₈ alkynyl, C₅₋₆ aryl, C₁₋₆heteroaryl, C₂₋₁₀ heterocyclyl, C₃₋₈ cycloalkyl, —CO—, and —CO—C₂₋₁₀heterocyclyl;wherein C₁₋₈ alkyl, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₂₋₁₀ heterocyclyl, C₃₋₈cycloalkyl, is optionally substituted with one or more of the groupsselected from hydrogen, C₁₋₆ alkyl, oxo (═O), C₃₋₈ cycloalkyl, halogen,OH, and cyano;Z represents a bond or is selected from the group consisting of C₁₋₈alkyl, C₁₋₈ alkenyl, C₁₋₈ alkynyl, C₇₋₁₂-alkylaryl, C₇₋₁₂-alkenylaryl,C₇₋₁₅-arylalkenyl, C₂₋₁₂-alkylheteroaryl, —CO—C₇₋₁₂ alkylaryl, —CO—C₇₋₁₂alkenylaryl, —CONR₆—C₁₋₈ alkyl, —NR₆CO—C₁₋₈ alkyl-, —NR₆—C₁₋₈ alkyl,—O—C₁₋₈ alkyl-, —CONR₆—C₅₋₆ aryl-, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₂₋₁₀heterocyclyl, —CO—C₂₋₁₀ heterocyclyl, —NR₆—CO—OC₁₋₈ alkyl, O—CO—NR₆—C₁₋₈alkyl, —NR₆CO—C₅₋₆ aryl-, —NR₆—C₅₋₆ aryl, —NR₆—C₁₋₆ heteroaryl, —C₁₋₈alkyl-O—C₅₋₆ aryl, —O—C₅₋₆ aryl, O—C₁₋₆ heteroaryl, —NR₆—CO—OC₅₋₆ aryl,—CONR₆—C₇₋₁₂ alkylaryl, —CONR₆—C₇₋₁₂ alkenylaryl, —SO₂—C₅₋₆ aryl,—SO₂—C₇₋₁₂ alkylaryl, —NR₆SO₂—C₇₋₁₂ alkylaryl, C₁₋₈ alkyl-CONR₆—C₅₋₆aryl, and O—CO—NR₆—C₅₋₆ aryl;R₆ is selected from the group consisting of hydrogen, C₁₋₈ alkyl, C₁₋₆haloalkyl, C₃₋₈ cycloalkyl, C₅₋₆ aryl, and C₁₋₆ heteroaryl, withheteroatoms selected from N, O, S;R₁ is selected from the group consisting of hydrogen, halogen hydroxy,nitro, cyano, azido, nitroso, oxo (═O), thioxo (═S), —SO₂—, amino,hydrazino, formyl, C₁₋₈ alkyl, C₁₋₈ haloalkyl, C₁₋₈ alkoxy, C₁₋₈haloalkoxy, C₇₋₁₂ arylalkoxy, C₃₋₈ cycloalkyl, C₃₋₈ cycloalkyloxy, C₅₋₆aryl, C₂₋₁₀ heterocyclyl, C₁₋₆ heteroaryl, alkylamino, —COOR_(a),—C(O)R_(b), —C(S)R_(a), —C(O)NR_(a)R_(b), —C(S)NR_(a)R_(b),—NR_(a)C(O)NR_(b)R_(c), NR_(a)C(S)NR_(b)R_(c), —N(R_(a))SOR_(b),—N(R_(a))SO₂R_(b), —NR_(a)C(O)OR_(b), —NR_(a)R_(b), —NR_(a)C(O)R_(b)—,—NR_(a)C(S)R_(b)—, —SONR_(a)R_(b)—, —SO₂NR_(a)R_(b)—, —OR_(a),—OR_(a)C(O)OR_(b)—, —OC(O)NR_(a)R_(b), OC(O)R_(a), —OC(O)NR_(a)R_(b)—,—R_(a)NR_(b)R_(c), —R_(a)OR_(b)—, —SR_(a), —SOR_(a) and —SO₂R_(a),wherein R_(a), R_(b) and R_(c) is independently selected from the groupconsisting of hydrogen, C₁₋₈ alkyl, C₃₋₈ cycloalkyl, C₅₋₆ aryl, C₇₋₁₅arylalkyl, C₂₋₁₀ heterocyclyl, C₁₋₆ heteroaryl, and C₂₋₁₂heteroarylalkyl with heteroatoms selected from N, O, S;wherein C₇₋₁₂ arylalkoxy, C₁₋₈ alkyl, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₂₋₁₀heterocyclyl, C₃₋₈ cycloalkyl, is optionally substituted with one ormore of the groups selected from hydrogen, C₁₋₆ alkyl, C₅₋₆ aryl, C₁₋₆heteroaryl, C₂₋₁₀ heterocyclyl, oxo (═O), C₃₋₈ cycloalkyl, halogen, OH,amino, and cyano;R₃ is selected from the group consisting of hydrogen, substituted orunsubstituted C₁₋₈ alkyl, and C₅₋₆ aryl;R₂ is selected from the group consisting of —OR₇, aniline, amino C₅₋₆aryl, and amino C₁₋₆ heteroaryl,wherein aniline, amino C₅₋₆ aryl, and amino C₁₋₆ heteroaryl, isoptionally substituted with one or more of the groups selected from C₁₋₈alkyl, halogen, OH, amino, and cyano;R₇ is selected from the group consisting of hydrogen, C₁₋₈ alkyl, C₅₋₆aryl, C₂₋₁₀ heterocyclyl and —COR₈, wherein R₈ is selected from thegroup consisting of C₁₋₈ alkyl, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₃₋₈cycloalkyl, and C₂₋₁₀ heterocyclyl.

In an embodiment of the present invention, there is provided a compoundof Formula I

their analogs, tautomeric forms, stereoisomers, polymorphs, solvates,intermediates, pharmaceutically acceptable salts, metabolites, andprodrugs thereof;whereinAr is selected from the group consisting of substituted or unsubstitutedC₅₋₆aryl, C₁₋₆ heteroaryl, and C₂₋₁₀ heterocyclyl with heteroatomsselected from N, O, S;W represents a bond or CR₄R₅, whereinR₄ and R₅ are independently selected from the group consisting ofhydrogen, substituted or unsubstituted C₁₋₈ alkyl, C₅₋₆ aryl, and C₁₋₆heteroaryl with heteroatoms selected from N, O, S;Y is a bond or is selected from the group consisting of substituted orunsubstituted C₁₋₈ alkyl, C₁₋₈ alkenyl, C₁₋₈ alkynyl, C₅₋₆ aryl, C₁₋₆heteroaryl, C₂₋₁₀ heterocyclyl, C₃₋₈ cycloalkyl, —CO—, and —CO—C₂₋₁₀heterocyclyl;wherein C₁₋₈ alkyl, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₂₋₁₀ heterocyclyl, C₃₋₈cycloalkyl, is optionally substituted with one or more of the groupsselected from hydrogen, C₁₋₆ alkyl, oxo (═O), C₃₋₈ cycloalkyl, halogen,OH, and cyano;Z represents a bond or is selected from the group consisting of C₁₋₈alkyl, C₁₋₈ alkenyl, C₁₋₈ alkynyl, C₇₋₁₂-alkylaryl, C₇₋₁₂-alkenylaryl,C₇₋₁₅-arylalkenyl, C₂₋₁₂-alkylheteroaryl, —CO—C₇₋₁₂ alkylaryl, —CO—C₇₋₁₂alkenylaryl, —CONR₆—C₁₋₈ alkyl, —NR₆CO—C₁₋₈ alkyl-, —NR₆—C₁₋₈ alkyl,—O—C₁₋₈ alkyl-, —CONR₆—C₅₋₆ aryl-, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₂₋₁₀heterocyclyl, —CO—C₂₋₁₀ heterocyclyl, —NR₆—CO—OC₁₋₈ alkyl, O—CO—NR₆—C₁₋₈alkyl, —NR₆CO—C₅₋₆ aryl-, —NR₆—C₅₋₆ aryl, —NR₆—C₁₋₆ heteroaryl, —C₁₋₈alkyl-O—C₅₋₆ aryl, —O—C₅₋₆ aryl, O—C₁₋₆ heteroaryl, —NR₆—CO—OC₅₋₆ aryl,—CONR₆—C₇₋₁₂ alkylaryl, —CONR₆—C₇₋₁₂ alkenylaryl, —SO₂—C₅₋₆ aryl,—SO₂—C₇₋₁₂ alkylaryl, —NR₆SO₂—C₇₋₁₂ alkylaryl, C₁₋₈ alkyl-CONR₆—C₅₋₆aryl, and O—CO—NR₆—C₅₋₆ aryl;R₆ is selected from the group consisting of hydrogen, C₁₋₈ alkyl, C₁₋₆haloalkyl, C₃₋₈ cycloalkyl, C₅₋₆ aryl, and C₁₋₆ heteroaryl, withheteroatoms selected from N, O, S;R₁ is selected from the group consisting of hydrogen, halogen hydroxy,nitro, cyano, azido, nitroso, oxo (═O), thioxo (═S), —SO₂—, amino,hydrazino, formyl, C₁₋₈ alkyl, C₁₋₈ haloalkyl, C₁₋₈ alkoxy, C₁₋₈haloalkoxy, C₇₋₁₂ arylalkoxy, C₃₋₈ cycloalkyl, C₃₋₈ cycloalkyloxy, C₅₋₆aryl, C₂₋₁₀ heterocyclyl, C₁₋₆ heteroaryl, alkylamino, —COOR_(a),—C(O)R_(b), —C(S)R_(a), —C(O)NR_(a)R_(b), —C(S)NR_(a)R_(b),—NR_(a)C(O)NR_(b)R_(c), NR_(a)C(S)NR_(b)R_(c), —N(R_(a))SOR_(b),—N(R_(a))SO₂R_(b), —NR_(a)C(O)OR_(b), —NR_(a)R_(b), —NR_(a)C(O)R_(b)—,—NR_(a)C(S)R_(b)—, —SONR_(a)R_(b)—, —SO₂NR_(a)R_(b)—, —OR_(a),—OR_(a)C(O)OR_(b)—, —OC(O)NR_(a)R_(b), OC(O)R_(a), —OC(O)NR_(a)R_(b)—,—R_(a)NR_(b)R_(c), —R_(a)OR_(b)—, —SR_(a), —SOR_(a) and —SO₂R_(a),wherein R_(a), R_(b) and R_(c) is independently selected from the groupconsisting of hydrogen, C₁₋₈ alkyl, C₃₋₈ cycloalkyl, C₅₋₆ aryl, C₇₋₁₅arylalkyl, C₂₋₁₀ heterocyclyl, C₁₋₆ heteroaryl, and C₂₋₁₂heteroarylalkyl with heteroatoms selected from N, O, S;wherein C₇₋₁₂ arylalkoxy, C₁₋₈ alkyl, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₂₋₁₀heterocyclyl, C₃₋₈ cycloalkyl, is optionally substituted with one ormore of the groups selected from hydrogen, C₁₋₆ alkyl, C₅₋₆ aryl, C₁₋₆heteroaryl, C₂₋₁₀ heterocyclyl, oxo (═O), C₃₋₈ cycloalkyl, halogen, OH,amino, and cyano;R₃ is selected from the group consisting of substituted or unsubstitutedC₁₋₈ alkyl, and C₅₋₆ aryl;R₂ is selected from the group consisting of —OR₇, aniline, amino C₅₋₆aryl, and amino C₁₋₆ heteroaryl,wherein aniline, amino C₅₋₆ aryl, and amino C₁₋₆ heteroaryl, isoptionally substituted with one or more of the groups selected from C₁₋₈alkyl, halogen, OH, amino, and cyano;R₇ is selected from the group consisting of hydrogen, C₁₋₈ alkyl, C₅₋₆aryl, C₂₋₁₀ heterocyclyl and —COR₈, wherein R₈ is selected from thegroup consisting of C₁₋₈ alkyl, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₃₋₈cycloalkyl, and C₂₋₁₀ heterocyclyl.

In an embodiment of the present invention, there is provided a compoundof Formula I

their analogs, tautomeric forms, stereoisomers, polymorphs, solvates,intermediates, pharmaceutically acceptable salts, metabolites, andprodrugs thereof;whereinAr is selected from the group consisting of substituted or unsubstitutedC₅₋₆aryl, C₁₋₆ heteroaryl, and C₂₋₁₀ heterocyclyl with heteroatomsselected from N, O, S;W represents a bond or CR₄R₅, whereinR₄ and R₅ are independently selected from the group consisting ofhydrogen, substituted or unsubstituted C₁₋₈ alkyl, C₅₋₆ aryl, and C₁₋₆heteroaryl with heteroatoms selected from N, O, S;Y is a bond or is selected from the group consisting of substituted orunsubstituted C₁₋₈ alkyl, C₁₋₈ alkenyl, C₁₋₈ alkynyl, C₅₋₆ aryl, C₁₋₆heteroaryl, C₂₋₁₀ heterocyclyl, C₃₋₈ cycloalkyl, —CO—, and —CO—C₂₋₁₀heterocyclyl;wherein C₁₋₈ alkyl, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₂₋₁₀ heterocyclyl, C₃₋₈cycloalkyl, is optionally substituted with one or more of the groupsselected from hydrogen, C₁₋₆ alkyl, oxo (═O), C₃₋₈ cycloalkyl, halogen,OH, and cyano;Z represents a bond or is selected from the group consisting of C₁₋₈alkyl, C₁₋₈ alkenyl, C₁₋₈ alkynyl, C₇₋₁₂-alkylaryl, C₇₋₁₂-alkenylaryl,C₇₋₁₅-arylalkenyl, C₂₋₁₂-alkylheteroaryl, —CO—C₇₋₁₂ alkylaryl, —CO—C₇₋₁₂alkenylaryl, —CONR₆—C₁₋₈ alkyl, —NR₆CO—C₁₋₈ alkyl-, —NR₆—C₁₋₈ alkyl,—O—C₁₋₈ alkyl-, —CONR₆—C₅₋₆ aryl-, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₂₋₁₀heterocyclyl, —CO—C₂₋₁₀ heterocyclyl, —NR₆—CO—OC₁₋₈ alkyl, O—CO—NR₆—C₁₋₈alkyl, —NR₆CO—C₅₋₆ aryl-, —NR₆—C₅₋₆ aryl, —NR₆—C₁₋₆ heteroaryl, —C₁₋₈alkyl-O—C₅₋₆ aryl, —O—C₅₋₆ aryl, O—C₁₋₆ heteroaryl, —NR₆—CO—OC₅₋₆ aryl,—CONR₆—C₇₋₁₂ alkylaryl, —CONR₆—C₇₋₁₂ alkenylaryl, —SO₂—C₅₋₆ aryl,—SO₂—C₇₋₁₂ alkylaryl, —NR₆SO₂—C₇₋₁₂ alkylaryl, C₁₋₈ alkyl-CONR₆—C₅₋₆aryl, and O—CO—NR₆—C₅₋₆ aryl;R₆ is selected from the group consisting of hydrogen, C₁₋₈ alkyl, C₁₋₆haloalkyl, C₃₋₈ cycloalkyl, C₅₋₆ aryl, and C₁₋₆ heteroaryl, withheteroatoms selected from N, O, S;R₁ is selected from the group consisting of hydrogen, halogen hydroxy,nitro, cyano, azido, nitroso, oxo (═O), thioxo (═S), —SO₂—, amino,hydrazino, formyl, C₁₋₈ alkyl, C₁₋₈ haloalkyl, C₁₋₈ alkoxy, C₁₋₈haloalkoxy, C₇₋₁₂ arylalkoxy, C₃₋₈ cycloalkyl, C₃₋₈ cycloalkyloxy, C₅₋₆aryl, C₂₋₁₀ heterocyclyl, C₁₋₆ heteroaryl, alkylamino, —COOR_(a),—C(O)R_(b), —C(S)R_(a), —C(O)NR_(a)R_(b), —C(S)NR_(a)R_(b),—NR_(a)C(O)NR_(b)R_(c), NR_(a)C(S)NR_(b)R_(c), —N(R_(a))SOR_(b),—N(R_(a))SO₂R_(b), —NR_(a)C(O)OR_(b), —NR_(a)R_(b), —NR_(a)C(O)R_(b)—,—NR_(a)C(S)R_(b)—, —SONR_(a)R_(b)—, —SO₂NR_(a)R_(b)—, —OR_(a),—OR_(a)C(O)OR_(b)—, —OC(O)NR_(a)R_(b), OC(O)R_(a), —OC(O)NR_(a)R_(b)—,—R_(a)NR_(b)R_(c), —R_(a)OR_(b)—, —SR_(a), —SOR_(a) and —SO₂R_(a),wherein R_(a), R_(b) and R_(c) is independently selected from the groupconsisting of hydrogen, C₁₋₈ alkyl, C₃₋₈ cycloalkyl, C₅₋₆ aryl, C₇₋₁₅arylalkyl, C₂₋₁₀ heterocyclyl, C₁₋₆ heteroaryl, and C₂₋₁₂heteroarylalkyl with heteroatoms selected from N, O, S;wherein C₇₋₁₂ arylalkoxy, C₁₋₈ alkyl, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₂₋₁₀heterocyclyl, C₃₋₈ cycloalkyl, is optionally substituted with one ormore of the groups selected from hydrogen, C₁₋₆ alkyl, C₅₋₆ aryl, C₁₋₆heteroaryl, C₂₋₁₀ heterocyclyl, oxo (═O), C₃₋₈ cycloalkyl, halogen, OH,amino, and cyano;R₃ is selected from the group consisting of hydrogen, and C₅₋₆ aryl;R₂ is selected from the group consisting of —OR₇, aniline, amino C₅₋₆aryl, and amino C₁₋₆ heteroaryl,wherein aniline, amino C₅₋₆ aryl, and amino C₁₋₆ heteroaryl, isoptionally substituted with one or more of the groups selected from C₁₋₈alkyl, halogen, OH, amino, and cyano;R₇ is selected from the group consisting of hydrogen, C₁₋₈ alkyl, C₅₋₆aryl, C₂₋₁₀ heterocyclyl and —COR₈, wherein R₈ is selected from thegroup consisting of C₁₋₈ alkyl, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₃₋₈cycloalkyl, and C₂₋₁₀ heterocyclyl.

In an embodiment of the present invention, there is provided a compoundof Formula I

their analogs, tautomeric forms, stereoisomers, polymorphs, solvates,intermediates, pharmaceutically acceptable salts, metabolites, andprodrugs thereof;whereinAr is selected from the group consisting of substituted or unsubstitutedC₅₋₆aryl, C₁₋₆ heteroaryl, and C₂₋₁₀ heterocyclyl with heteroatomsselected from N, O, S;W represents CR₄R₅, whereinR₄ and R₅ are independently selected from the group consisting ofhydrogen, substituted or unsubstituted C₁₋₈ alkyl, C₅₋₆ aryl, and C₁₋₆heteroaryl with heteroatoms selected from N, O, S;Y is a bond or is selected from the group consisting of substituted orunsubstituted C₁₋₈ alkyl, C₁₋₈ alkenyl, C₁₋₈ alkynyl, C₅₋₆ aryl, C₁₋₆heteroaryl, C₂₋₁₀ heterocyclyl, C₃₋₈ cycloalkyl, —CO—, and —CO—C₂₋₁₀heterocyclyl;wherein C₁₋₈ alkyl, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₂₋₁₀ heterocyclyl, C₃₋₈cycloalkyl, is optionally substituted with one or more of the groupsselected from hydrogen, C₁₋₆ alkyl, oxo (═O), C₃₋₈ cycloalkyl, halogen,OH, and cyano;Z represents a bond or is selected from the group consisting of C₁₋₈alkyl, C₁₋₈ alkenyl, C₁₋₈ alkynyl, C₇₋₁₂-alkylaryl, C₇₋₁₂-alkenylaryl,C₇₋₁₅-arylalkenyl, C₂₋₁₂-alkylheteroaryl, —CO—C₇₋₁₂ alkylaryl, —CO—C₇₋₁₂alkenylaryl, —CONR₆—C₁₋₈ alkyl, —NR₆CO—C₁₋₈ alkyl-, —NR₆—C₁₋₈ alkyl,—O—C₁₋₈ alkyl-, —CONR₆—C₅₋₆ aryl-, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₂₋₁₀heterocyclyl, —CO—C₂₋₁₀ heterocyclyl, —NR₆—CO—OC₁₋₈ alkyl, O—CO—NR₆—C₁₋₈alkyl, —NR₆CO—C₅₋₆ aryl-, —NR₆—C₅₋₆ aryl, —NR₆—C₁₋₆ heteroaryl, —C₁₋₈alkyl-O—C₅₋₆ aryl, —O—C₅₋₆ aryl, O—C₁₋₆ heteroaryl, —NR₆—CO—OC₅₋₆ aryl,—CONR₆—C₇₋₁₂ alkylaryl, —CONR₆—C₇₋₁₂ alkenylaryl, —SO₂—C₅₋₆ aryl,—SO₂—C₇₋₁₂ alkylaryl, —NR₆SO₂—C₇₋₁₂ alkylaryl, C₁₋₈ alkyl-CONR₆—C₅₋₆aryl, and O—CO—NR₆—C₅₋₆ aryl;R₆ is selected from the group consisting of hydrogen, C₁₋₈ alkyl, C₁₋₆haloalkyl, C₃₋₈ cycloalkyl, C₅₋₆ aryl, and C₁₋₆ heteroaryl, withheteroatoms selected from N, O, S;R₁ is selected from the group consisting of hydrogen, halogen hydroxy,nitro, cyano, azido, nitroso, oxo (═O), thioxo (═S), —SO₂—, amino,hydrazino, formyl, C₁₋₈ alkyl, C₁₋₈ haloalkyl, C₁₋₈ alkoxy, C₁₋₈haloalkoxy, C₇₋₁₂ arylalkoxy, C₃₋₈ cycloalkyl, C₃₋₈ cycloalkyloxy, C₅₋₆aryl, C₂₋₁₀ heterocyclyl, C₁₋₆ heteroaryl, alkylamino, —COOR_(a),—C(O)R_(b), —C(S)R_(a), —C(O)NR_(a)R_(b), —C(S)NR_(a)R_(b),—NR_(a)C(O)NR_(b)R_(c), NR_(a)C(S)NR_(b)R_(c), —N(R_(a))SOR_(b),—N(R_(a))SO₂R_(b), —NR_(a)C(O)OR_(b), —NR_(a)R_(b), —NR_(a)C(O)R_(b)—,—NR_(a)C(S)R_(b)—, —SONR_(a)R_(b)—, —SO₂NR_(a)R_(b)—, —OR_(a),—OR_(a)C(O)OR_(b)—, —OC(O)NR_(a)R_(b), OC(O)R_(a), —OC(O)NR_(a)R_(b)—,—R_(a)NR_(b)R_(c), —R_(a)OR_(b)—, —SR_(a), —SOR_(a) and —SO₂R_(a),wherein R_(a), R_(b) and R_(c) is independently selected from the groupconsisting of hydrogen, C₁₋₈ alkyl, C₃₋₈ cycloalkyl, C₅₋₆ aryl, C₇₋₁₅arylalkyl, C₂₋₁₀ heterocyclyl, C₁₋₆ heteroaryl, and C₂₋₁₂heteroarylalkyl with heteroatoms selected from N, O, S;wherein C₇₋₁₂ arylalkoxy, C₁₋₈ alkyl, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₂₋₁₀heterocyclyl, C₃₋₈ cycloalkyl, is optionally substituted with one ormore of the groups selected from hydrogen, C₁₋₆ alkyl, C₅₋₆ aryl, C₁₋₆heteroaryl, C₂₋₁₀ heterocyclyl, oxo (═O), C₃₋₈ cycloalkyl, halogen, OH,amino, and cyano;R₃ is selected from the group consisting of hydrogen, substituted orunsubstituted C₁₋₈ alkyl, and C₅₋₆ aryl;R₂ is selected from the group consisting of —OR₇, aniline, amino C₅₋₆aryl, and amino C₁₋₆ heteroaryl,wherein aniline, amino C₅₋₆ aryl, and amino C₁₋₆ heteroaryl, isoptionally substituted with one or more of the groups selected from C₁₋₈alkyl, halogen, OH, amino, and cyano;R₇ is selected from the group consisting of hydrogen, C₁₋₈ alkyl, C₅₋₆aryl, C₂₋₁₀ heterocyclyl and —COR₈, wherein R₈ is selected from thegroup consisting of C₁₋₈ alkyl, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₃₋₈cycloalkyl, and C₂₋₁₀ heterocyclyl.

In an embodiment of the present invention, there is provided a compoundof Formula I

their analogs, tautomeric forms, stereoisomers, polymorphs, solvates,intermediates, pharmaceutically acceptable salts, metabolites, andprodrugs thereof;whereinAr is selected from the group consisting of substituted or unsubstitutedC₅₋₆ aryl, C₁₋₆ heteroaryl, and C₂₋₁₀ heterocyclyl with heteroatomsselected from N, O, S;W represents a bond or CR₄R₅, whereinR₄ and R₅ are independently selected from the group consisting ofsubstituted or unsubstituted C₁₋₈ alkyl, C₅₋₆ aryl, and C₁₋₆ heteroarylwith heteroatoms selected from N, O, S;Y is a bond or is selected from the group consisting of substituted orunsubstituted C₁₋₈ alkyl, C₁₋₈ alkenyl, C₁₋₈ alkynyl, C₅₋₆ aryl, C₁₋₆heteroaryl, C₂₋₁₀ heterocyclyl, C₃₋₈ cycloalkyl, —CO—, and —CO—C₂₋₁₀heterocyclyl;wherein C₁₋₈ alkyl, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₂₋₁₀ heterocyclyl, C₃₋₈cycloalkyl, is optionally substituted with one or more of the groupsselected from hydrogen, C₁₋₆ alkyl, oxo (═O), C₃₋₈ cycloalkyl, halogen,OH, and cyano;Z represents a bond or is selected from the group consisting of C₁₋₈alkyl, C₁₋₈ alkenyl, C₁₋₈ alkynyl, C₇₋₁₂-alkylaryl, C₇₋₁₂-alkenylaryl,C₇₋₁₅-arylalkenyl, C₂₋₁₂-alkylheteroaryl, —CO—C₇₋₁₂ alkylaryl, —CO—C₇₋₁₂alkenylaryl, —CONR₆—C₁₋₈ alkyl, —NR₆CO—C₁₋₈ alkyl-, —NR₆—C₁₋₈ alkyl,—O—C₁₋₈ alkyl-, —CONR₆—C₅₋₆ aryl-, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₂₋₁₀heterocyclyl, —CO—C₂₋₁₀ heterocyclyl, —NR₆—CO—OC₁₋₈ alkyl, O—CO—NR₆—C₁₋₈alkyl, —NR₆CO—C₅₋₆ aryl-, —NR₆—C₅₋₆ aryl, —NR₆—C₁₋₆ heteroaryl, —C₁₋₈alkyl-O—C₅₋₆ aryl, —O—C₅₋₆ aryl, O—C₁₋₆ heteroaryl, —NR₆—CO—OC₅₋₆ aryl,—CONR₆—C₇₋₁₂ alkylaryl, —CONR₆—C₇₋₁₂ alkenylaryl, —SO₂—C₅₋₆ aryl,—SO₂—C₇₋₁₂ alkylaryl, —NR₆SO₂—C₇₋₁₂ alkylaryl, C₁₋₈ alkyl-CONR₆—C₅₋₆aryl, and O—CO—NR₆—C₅₋₆ aryl;R₆ is selected from the group consisting of hydrogen, C₁₋₈ alkyl, C₁₋₆haloalkyl, C₃₋₈ cycloalkyl, C₅₋₆ aryl, and C₁₋₆ heteroaryl, withheteroatoms selected from N, O, S;R₁ is selected from the group consisting of hydrogen, halogen hydroxy,nitro, cyano, azido, nitroso, oxo (═O), thioxo (═S), —SO₂—, amino,hydrazino, formyl, C₁₋₈ alkyl, C₁₋₈ haloalkyl, C₁₋₈ alkoxy, C₁₋₈haloalkoxy, C₇₋₁₂ arylalkoxy, C₃₋₈ cycloalkyl, C₃₋₈ cycloalkyloxy, C₅₋₆aryl, C₂₋₁₀ heterocyclyl, C₁₋₆ heteroaryl, alkylamino, —COOR_(a),—C(O)R_(b), —C(S)R_(a), —C(O)NR_(a)R_(b), —C(S)NR_(a)R_(b),—NR_(a)C(O)NR_(b)R_(c), NR_(a)C(S)NR_(b)R_(c), —N(R_(a))SOR_(b),—N(R_(a))SO₂R_(b), —NR_(a)C(O)OR_(b), —NR_(a)R_(b), —NR_(a)C(O)R_(b)—,—NR_(a)C(S)R_(b)—, —SONR_(a)R_(b)—, —SO₂NR_(a)R_(b)—, —OR_(a),—OR_(a)C(O)OR_(b)—, —OC(O)NR_(a)R_(b), OC(O)R_(a), —OC(O)NR_(a)R_(b)—,—R_(a)NR_(b)R_(c), —R_(a)OR_(b)—, —SR_(a), —SOR_(a) and —SO₂R_(a),wherein R_(a), R_(b) and R_(c) is independently selected from the groupconsisting of hydrogen, C₁₋₈ alkyl, C₃₋₈ cycloalkyl, C₅₋₆ aryl, C₇₋₁₅arylalkyl, C₂₋₁₀ heterocyclyl, C₁₋₆ heteroaryl, and C₂₋₁₂heteroarylalkyl with heteroatoms selected from N, O, S;wherein C₇₋₁₂ arylalkoxy, C₁₋₈ alkyl, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₂₋₁₀heterocyclyl, C₃₋₈ cycloalkyl, is optionally substituted with one ormore of the groups selected from hydrogen, C₁₋₆ alkyl, C₅₋₆ aryl, C₁₋₆heteroaryl, C₂₋₁₀ heterocyclyl, oxo (═O), C₃₋₈ cycloalkyl, halogen, OH,amino, and cyano;R₃ is selected from the group consisting of hydrogen, substituted orunsubstituted C₁₋₈ alkyl, and C₅₋₆ aryl;R₂ is selected from the group consisting of —OR₇, aniline, amino C₅₋₆aryl, and amino C₁₋₆ heteroaryl,wherein aniline, amino C₅₋₆ aryl, and amino C₁₋₆ heteroaryl, isoptionally substituted with one or more of the groups selected from C₁₋₈alkyl, halogen, OH, amino, and cyano;R₇ is selected from the group consisting of hydrogen, C₁₋₈ alkyl, C₅₋₆aryl, C₂₋₁₀ heterocyclyl and —COR₈, wherein R₈ is selected from thegroup consisting of C₁₋₈ alkyl, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₃₋₈cycloalkyl, and C₂₋₁₀ heterocyclyl.

In an embodiment of the present invention, there is provided a compoundof Formula I

their analogs, tautomeric forms, stereoisomers, polymorphs, solvates,intermediates, pharmaceutically acceptable salts, metabolites, andprodrugs thereof;whereinAr is selected from the group consisting of substituted or unsubstitutedC₅₋₆aryl, C₁₋₆ heteroaryl, and C₂₋₁₀ heterocyclyl with heteroatomsselected from N, O, S;W represents a bond or CR₄R₅, whereinR₄ and R₅ are independently selected from the group consisting ofhydrogen, C₅₋₆ aryl, and C₁₋₆ heteroaryl with heteroatoms selected fromN, O, S;Y is a bond or is selected from the group consisting of substituted orunsubstituted C₁₋₈ alkyl, C₁₋₈ alkenyl, C₁₋₈ alkynyl, C₅₋₆ aryl, C₁₋₆heteroaryl, C₂₋₁₀ heterocyclyl, C₃₋₈ cycloalkyl, —CO—, and —CO—C₂₋₁₀heterocyclyl;wherein C₁₋₈ alkyl, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₂₋₁₀ heterocyclyl, C₃₋₈cycloalkyl, is optionally substituted with one or more of the groupsselected from hydrogen, C₁₋₆ alkyl, oxo (═O), C₃₋₈ cycloalkyl, halogen,OH, and cyano;Z represents a bond or is selected from the group consisting of C₁₋₈alkyl, C₁₋₈ alkenyl, C₁₋₈ alkynyl, C₇₋₁₂-alkylaryl, C₇₋₁₂-alkenylaryl,C₇₋₁₅-arylalkenyl, C₂₋₁₂-alkylheteroaryl, —CO—C₇₋₁₂ alkylaryl, —CO—C₇₋₁₂alkenylaryl, —CONR₆—C₁₋₈ alkyl, —NR₆CO—C₁₋₈ alkyl-, —NR₆—C₁₋₈ alkyl,—O—C₈ alkyl-, —CONR₆—C₅₋₆ aryl-, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₂₋₁₀heterocyclyl, —CO—C₂₋₁₀ heterocyclyl, —NR₆—CO—OC₁₋₈ alkyl, O—CO—NR₆—C₁₋₈alkyl, —NR₆CO—C₅₋₆ aryl-, —NR₆—C₅₋₆ aryl, —NR₆—C₁₋₆ heteroaryl, —C₁₋₈alkyl-O—C₅₋₆ aryl, —O—C₅₋₆ aryl, O—C₁₋₆ heteroaryl, —NR₆—CO—OC₅₋₆ aryl,—CONR₆—C₇₋₁₂ alkylaryl, —CONR₆—C₇₋₁₂ alkenylaryl, —SO₂—C₅₋₆ aryl,—SO₂—C₇₋₁₂ alkylaryl, —NR₆SO₂—C₇₋₁₂ alkylaryl, C₁₋₈ alkyl-CONR₆—C₅₋₆aryl, and O—CO—NR₆—C₅₋₆ aryl;R₆ is selected from the group consisting of hydrogen, C₁₋₈ alkyl, C₁₋₆haloalkyl, C₃₋₈ cycloalkyl, C₅₋₆ aryl, and C₁₋₆ heteroaryl, withheteroatoms selected from N, O, S;R₁ is selected from the group consisting of hydrogen, halogen hydroxy,nitro, cyano, azido, nitroso, oxo (═O), thioxo (═S), —SO₂—, amino,hydrazino, formyl, C₁₋₈ alkyl, C₁₋₈ haloalkyl, C₁₋₈ alkoxy, C₁₋₈haloalkoxy, C₇₋₁₂ arylalkoxy, C₃₋₈ cycloalkyl, C₃₋₈ cycloalkyloxy, C₅₋₆aryl, C₂₋₁₀ heterocyclyl, C₁₋₆ heteroaryl, alkylamino, —COOR_(a),—C(O)R_(b), —C(S)R_(a), —C(O)NR_(a)R_(b), —C(S)NR_(a)R_(b),—NR_(a)C(O)NR_(b)R_(c), NR_(a)C(S)NR_(b)R_(c), —N(R_(a))SOR_(b),—N(R_(a))SO₂R_(b), —NR_(a)C(O)OR_(b), —NR_(a)R_(b), —NR_(a)C(O)R_(b)—,—NR_(a)C(S)R_(b)—, —SONR_(a)R_(b)—, —SO₂NR_(a)R_(b)—, —OR_(a),—OR_(a)C(O)OR_(b)—, —OC(O)NR_(a)R_(b), OC(O)R_(a), —OC(O)NR_(a)R_(b)—,—R_(a)NR_(b)R_(c), —R_(a)OR_(b)—, —SR_(a), —SOR_(a) and —SO₂R_(a),wherein R_(a), R_(b) and R_(c) is independently selected from the groupconsisting of hydrogen, C₁₋₈ alkyl, C₃₋₈ cycloalkyl, C₅₋₆ aryl, C₇₋₁₅arylalkyl, C₂₋₁₀ heterocyclyl, C₁₋₆ heteroaryl, and C₂₋₁₂heteroarylalkyl with heteroatoms selected from N, O, S;wherein C₇₋₁₂ arylalkoxy, C₁₋₈ alkyl, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₂₋₁₀heterocyclyl, C₃₋₈ cycloalkyl, is optionally substituted with one ormore of the groups selected from hydrogen, C₁₋₆ alkyl, C₅₋₆ aryl, C₁₋₆heteroaryl, C₂₋₁₀ heterocyclyl, oxo (═O), C₃₋₈ cycloalkyl, halogen, OH,amino, and cyano;R₃ is selected from the group consisting of hydrogen, substituted orunsubstituted C₁₋₈ alkyl, and C₅₋₆ aryl;R₂ is selected from the group consisting of —OR₇, aniline, amino C₅₋₆aryl, and amino C₁₋₆ heteroaryl,wherein aniline, amino C₅₋₆ aryl, and amino C₁₋₆ heteroaryl, isoptionally substituted with one or more of the groups selected from C₁₋₈alkyl, halogen, OH, amino, and cyano;R₇ is selected from the group consisting of hydrogen, C₁₋₈ alkyl, C₅₋₆aryl, C₂₋₁₀ heterocyclyl and —COR₈, wherein R₈ is selected from thegroup consisting of C₁₋₈ alkyl, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₃₋₈cycloalkyl, and C₂₋₁₀ heterocyclyl.

In an embodiment of the present invention, there is provided a compoundof Formula I

their analogs, tautomeric forms, stereoisomers, polymorphs, solvates,intermediates, pharmaceutically acceptable salts, metabolites, andprodrugs thereof;whereinAr is selected from the group consisting of substituted or unsubstitutedC₅₋₆aryl, C₁₋₆ heteroaryl, and C₂₋₁₀ heterocyclyl with heteroatomsselected from N, O, S;W represents a bond or CR₄R₅, whereinR₄ and R₅ are independently selected from the group consisting ofhydrogen, substituted or unsubstituted C₁₋₈ alkyl, C₅₋₆ aryl, and C₁₋₆heteroaryl with heteroatoms selected from N, O, S;Y is a bond or is selected from the group consisting of substituted orunsubstituted C₁₋₈ alkyl, C₁₋₈ alkenyl, C₁₋₈ alkynyl, C₁₋₆ heteroaryl,C₂₋₁₀ heterocyclyl, C₃₋₈ cycloalkyl, —CO—, and —CO—C₂₋₁₀ heterocyclyl;wherein C₁₋₈ alkyl, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₂₋₁₀ heterocyclyl, C₃₋₈cycloalkyl, is optionally substituted with one or more of the groupsselected from hydrogen, C₁₋₆ alkyl, oxo (═O), C₃₋₈ cycloalkyl, halogen,OH, and cyano;Z represents a bond or is selected from the group consisting of C₁₋₈alkyl, C₁₋₈ alkenyl, C₁₋₈ alkynyl, C₇₋₁₂-alkylaryl, C₇₋₁₂-alkenylaryl,C₇₋₁₅-arylalkenyl, C₂₋₁₂-alkylheteroaryl, —CO—C₇₋₁₂ alkylaryl, —CO—C₇₋₁₂alkenylaryl, —CONR₆—C₁₋₈ alkyl, —NR₆CO—C₁₋₈ alkyl-, —NR₆—C₁₋₈ alkyl,—O—C₁₋₈ alkyl-, —CONR₆—C₅₋₆ aryl-, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₂₋₁₀heterocyclyl, —CO—C₂₋₁₀ heterocyclyl, —NR₆—CO—OC₁₋₈ alkyl, O—CO—NR₆—C₁₋₈alkyl, —NR₆CO—C₅₋₆ aryl-, —NR₆—C₅₋₆ aryl, —NR₆—C₁₋₆ heteroaryl, —C₁₋₈alkyl-O—C₅₋₆ aryl, —O—C₅₋₆ aryl, O—C₁₋₆ heteroaryl, —NR₆—CO—OC₅₋₆ aryl,—CONR₆—C₇₋₁₂ alkylaryl, —CONR₆—C₇₋₁₂ alkenylaryl, —SO₂—C₅₋₆ aryl,—SO₂—C₇₋₁₂ alkylaryl, —NR₆SO₂—C₇₋₁₂ alkylaryl, C₁₋₈ alkyl-CONR₆—C₅₋₆aryl, and O—CO—NR₆—C₅₋₆ aryl;R₆ is selected from the group consisting of hydrogen, C₁₋₈ alkyl, C₁₋₆haloalkyl, C₃₋₈ cycloalkyl, C₅₋₆ aryl, and C₁₋₆ heteroaryl, withheteroatoms selected from N, O, S;R₁ is selected from the group consisting of hydrogen, halogen hydroxy,nitro, cyano, azido, nitroso, oxo (═O), thioxo (═S), —SO₂—, amino,hydrazino, formyl, C₁₋₈ alkyl, C₁₋₈ haloalkyl, C₁₋₈ alkoxy, C₁₋₈haloalkoxy, C₇₋₁₂ arylalkoxy, C₃₋₈ cycloalkyl, C₃₋₈ cycloalkyloxy, C₅₋₆aryl, C₂₋₁₀ heterocyclyl, C₁₋₆ heteroaryl, alkylamino, —COOR_(a),—C(O)R_(b), —C(S)R_(a), —C(O)NR_(a)R_(b), —C(S)NR_(a)R_(b),—NR_(a)C(O)NR_(b)R_(c), NR_(a)C(S)NR_(b)R_(c), —N(R_(a))SOR_(b),—N(R_(a))SO₂R_(b), —NR_(a)C(O)OR_(b), —NR_(a)R_(b), —NR_(a)C(O)R_(b)—,—NR_(a)C(S)R_(b)—, —SONR_(a)R_(b)—, —SO₂NR_(a)R_(b)—, —OR_(a),—OR_(a)C(O)OR_(b)—, —OC(O)NR_(a)R_(b), OC(O)R_(a), —OC(O)NR_(a)R_(b)—,—R_(a)NR_(b)R_(c), —R_(a)OR_(b)—, —SR_(a), —SOR_(a) and —SO₂R_(a),wherein R_(a), R_(b) and R_(c) is independently selected from the groupconsisting of hydrogen, C₁₋₈ alkyl, C₃₋₈ cycloalkyl, C₅₋₆ aryl, C₇₋₁₅arylalkyl, C₂₋₁₀ heterocyclyl, C₁₋₆ heteroaryl, and C₂₋₁₂heteroarylalkyl with heteroatoms selected from N, O, S;wherein C₇₋₁₂ arylalkoxy, C₁₋₈ alkyl, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₂₋₁₀heterocyclyl, C₃₋₈ cycloalkyl, is optionally substituted with one ormore of the groups selected from hydrogen, C₁₋₆ alkyl, C₅₋₆ aryl, C₁₋₆heteroaryl, C₂₋₁₀ heterocyclyl, oxo (═O), C₃₋₈ cycloalkyl, halogen, OH,amino, and cyano;R₃ is selected from the group consisting of hydrogen, substituted orunsubstituted C₁₋₈ alkyl, and C₅₋₆ aryl;R₂ is selected from the group consisting of —OR₇, aniline, amino C₅₋₆aryl, and amino C₁₋₆ heteroaryl,wherein aniline, amino C₅₋₆ aryl, and amino C₁₋₆ heteroaryl, isoptionally substituted with one or more of the groups selected from C₁₋₈alkyl, halogen, OH, amino, and cyano;R₇ is selected from the group consisting of hydrogen, C₁₋₈ alkyl, C₅₋₆aryl, C₂₋₁₀ heterocyclyl and —COR₈, wherein R₈ is selected from thegroup consisting of C₁₋₈ alkyl, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₃₋₈cycloalkyl, and C₂₋₁₀ heterocyclyl.

In an embodiment of the present invention, there is provided a compoundof Formula I

their analogs, tautomeric forms, stereoisomers, polymorphs, solvates,intermediates, pharmaceutically acceptable salts, metabolites, andprodrugs thereof;whereinAr is selected from the group consisting of substituted or unsubstitutedC₅₋₆aryl, C₁₋₆ heteroaryl, and C₂₋₁₀ heterocyclyl with heteroatomsselected from N, O, S;W represents a bond or CR₄R₅, whereinR₄ and R₅ are independently selected from the group consisting ofhydrogen, substituted or unsubstituted C₁₋₈ alkyl, C₅₋₆ aryl, and C₁₋₆heteroaryl with heteroatoms selected from N, O, S;Y is a bond or is selected from the group consisting of substituted orunsubstituted C₁₋₈ alkyl, C₁₋₈ alkenyl, C₁₋₈ alkynyl, C₅₋₆ aryl, C₁₋₆heteroaryl, C₃₋₈ cycloalkyl, —CO—, and —CO—C₂₋₁₀ heterocyclyl;wherein C₁₋₈ alkyl, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₂₋₁₀ heterocyclyl, C₃₋₈cycloalkyl, is optionally substituted with one or more of the groupsselected from hydrogen, C₁₋₆ alkyl, oxo (═O), C₃₋₈ cycloalkyl, halogen,OH, and cyano;Z represents a bond or is selected from the group consisting of C₁₋₈alkyl, C₁₋₈ alkenyl, C₁₋₈ alkynyl, C₇₋₁₂-alkylaryl, C₇₋₁₂-alkenylaryl,C₇₋₁₅-arylalkenyl, C₂₋₁₂-alkylheteroaryl, —CO—C₇₋₁₂ alkylaryl, —CO—C₇₋₁₂alkenylaryl, —CONR₆—C₁₋₈ alkyl, —NR₆CO—C₁₋₈ alkyl-, —NR₆—C₁₋₈ alkyl,—O—C₁₋₈ alkyl-, —CONR₆—C₅₋₆ aryl-, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₂₋₁₀heterocyclyl, —CO—C₂₋₁₀ heterocyclyl, —NR₆—CO—OC₁₋₈ alkyl, O—CO—NR₆—C₁₋₈alkyl, —NR₆CO—C₅₋₆ aryl-, —NR₆—C₅₋₆ aryl, —NR₆—C₁₋₆ heteroaryl, —C₁₋₈alkyl-O—C₅₋₆ aryl, —O—C₅₋₆ aryl, O—C₁₋₆ heteroaryl, —NR₆—CO—OC₅₋₆ aryl,—CONR₆—C₇₋₁₂ alkylaryl, —CONR₆—C₇₋₁₂ alkenylaryl, —SO₂—C₅₋₆ aryl,—SO₂—C₇₋₁₂ alkylaryl, —NR₆SO₂—C₇₋₁₂ alkylaryl, C₁₋₈ alkyl-CONR₆—C₅₋₆aryl, and O—CO—NR₆—C₅₋₆ aryl;R₆ is selected from the group consisting of hydrogen, C₁₋₈ alkyl, C₁₋₆haloalkyl, C₃₋₈ cycloalkyl, C₅₋₆ aryl, and C₁₋₆ heteroaryl, withheteroatoms selected from N, O, S;R₁ is selected from the group consisting of hydrogen, halogen hydroxy,nitro, cyano, azido, nitroso, oxo (═O), thioxo (═S), —SO₂—, amino,hydrazino, formyl, C₁₋₈ alkyl, C₁₋₈ haloalkyl, C₁₋₈ alkoxy, C₁₋₈haloalkoxy, C₇₋₁₂ arylalkoxy, C₃₋₈ cycloalkyl, C₃₋₈ cycloalkyloxy, C₅₋₆aryl, C₂₋₁₀ heterocyclyl, C₁₋₆ heteroaryl, alkylamino, —COOR_(a),—C(O)R_(b), —C(S)R_(a), —C(O)NR_(a)R_(b), —C(S)NR_(a)R_(b),—NR_(a)C(O)NR_(b)R_(c), NR_(a)C(S)NR_(b)R_(c), —N(R_(a))SOR_(b),—N(R_(a))SO₂R_(b), —NR_(a)C(O)OR_(b), —NR_(a)R_(b), —NR_(a)C(O)R_(b)—,—NR_(a)C(S)R_(b)—, —SONR_(a)R_(b)—, —SO₂NR_(a)R_(b)—, —OR_(a),—OR_(a)C(O)OR_(b)—, —OC(O)NR_(a)R_(b), OC(O)R_(a), —OC(O)NR_(a)R_(b)—,—R_(a)NR_(b)R_(c), —R_(a)OR_(b)—, —SR_(a), —SOR_(a) and —SO₂R_(a),wherein R_(a), R_(b) and R_(c) is independently selected from the groupconsisting of hydrogen, C₁₋₈ alkyl, C₃₋₈ cycloalkyl, C₅₋₆ aryl, C₇₋₁₅arylalkyl, C₂₋₁₀ heterocyclyl, C₁₋₆ heteroaryl, and C₂₋₁₂heteroarylalkyl with heteroatoms selected from N, O, S;wherein C₇₋₁₂ arylalkoxy, C₁₋₈ alkyl, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₂₋₁₀heterocyclyl, C₃₋₈ cycloalkyl, is optionally substituted with one ormore of the groups selected from hydrogen, C₁₋₆ alkyl, C₅₋₆ aryl, C₁₋₆heteroaryl, C₂₋₁₀ heterocyclyl, oxo (═O), C₃₋₈ cycloalkyl, halogen, OH,amino, and cyano;R₃ is selected from the group consisting of hydrogen, substituted orunsubstituted C₁₋₈ alkyl, and C₅₋₆ aryl;R₂ is selected from the group consisting of —OR₇, aniline, amino C₅₋₆aryl, and amino C₁₋₆ heteroaryl,wherein aniline, amino C₅₋₆ aryl, and amino C₁₋₆ heteroaryl, isoptionally substituted with one or more of the groups selected from C₁₋₈alkyl, halogen, OH, amino, and cyano;R₇ is selected from the group consisting of hydrogen, C₁₋₈ alkyl, C₅₋₆aryl, C₂₋₁₀ heterocyclyl and —COR₈, wherein R₈ is selected from thegroup consisting of C₁₋₈ alkyl, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₃₋₈cycloalkyl, and C₂₋₁₀ heterocyclyl.

In an embodiment of the present invention, there is provided a compoundof Formula I

their analogs, tautomeric forms, stereoisomers, polymorphs, solvates,intermediates, pharmaceutically acceptable salts, metabolites, andprodrugs thereof;whereinAr is selected from the group consisting of substituted or unsubstitutedC₅₋₆aryl, C₁₋₆ heteroaryl, and C₂₋₁₀ heterocyclyl with heteroatomsselected from N, O, S;W represents a bond or CR₄R₅, whereinR₄ and R₅ are independently selected from the group consisting ofhydrogen, substituted or unsubstituted C₁₋₈ alkyl, C₅₋₆ aryl, and C₁₋₆heteroaryl with heteroatoms selected from N, O, S;Y is selected from the group consisting of substituted or unsubstitutedC₁₋₈ alkyl, C₁₋₈ alkenyl, C₁₋₈ alkynyl, C₅₋₆ aryl, C₁₋₆ heteroaryl,C₂₋₁₀ heterocyclyl, C₃₋₈ cycloalkyl, —CO—, and —CO—C₂₋₁₀ heterocyclyl;wherein C₁₋₈ alkyl, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₂₋₁₀ heterocyclyl, C₃₋₈cycloalkyl, is optionally substituted with one or more of the groupsselected from hydrogen, C₁₋₆ alkyl, oxo (═O), C₃₋₈ cycloalkyl, halogen,OH, and cyano;Z represents a bond or is selected from the group consisting of C₁₋₈alkyl, C₁₋₈ alkenyl, C₁₋₈ alkynyl, C₇₋₁₂-alkylaryl, C₇₋₁₂-alkenylaryl,C₇₋₁₅-arylalkenyl, C₂₋₁₂-alkylheteroaryl, —CO—C₇₋₁₂ alkylaryl, —CO—C₇₋₁₂alkenylaryl, —CONR₆—C₁₋₈ alkyl, —NR₆CO—C₁₋₈ alkyl-, —NR₆—C₁₋₈ alkyl,—O—C₁₋₈ alkyl-, —CONR₆—C₅₋₆ aryl-, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₂₋₁₀heterocyclyl, —CO—C₂₋₁₀ heterocyclyl, —NR₆—CO—OC₁₋₈ alkyl, O—CO—NR₆—C₁₋₈alkyl, —NR₆CO—C₅₋₆ aryl-, —NR₆—C₅₋₆ aryl, —NR₆—C₁₋₆ heteroaryl, —C₁₋₈alkyl-O—C₅₋₆ aryl, —O—C₅₋₆ aryl, O—C₁₋₆ heteroaryl, —NR₆—CO—OC₅₋₆ aryl,—CONR₆—C₇₋₁₂ alkylaryl, —CONR₆—C₇₋₁₂ alkenylaryl, —SO₂—C₅₋₆ aryl,—SO₂—C₇₋₁₂ alkylaryl, —NR₆SO₂—C₇₋₁₂ alkylaryl, C₁₋₈ alkyl-CONR₆—C₅₋₆aryl, and O—CO—NR₆—C₅₋₆ aryl;R₆ is selected from the group consisting of hydrogen, C₁₋₈ alkyl, C₁₋₆haloalkyl, C₃₋₈ cycloalkyl, C₅₋₆ aryl, and C₁₋₆ heteroaryl, withheteroatoms selected from N, O, S;R₁ is selected from the group consisting of hydrogen, halogen hydroxy,nitro, cyano, azido, nitroso, oxo (═O), thioxo (═S), —SO₂—, amino,hydrazino, formyl, C₁₋₈ alkyl, C₁₋₈ haloalkyl, C₁₋₈ alkoxy, C₁₋₈haloalkoxy, C₇₋₁₂ arylalkoxy, C₃₋₈ cycloalkyl, C₃₋₈ cycloalkyloxy, C₅₋₆aryl, C₂₋₁₀ heterocyclyl, C₁₋₆ heteroaryl, alkylamino, —COOR_(a),—C(O)R_(b), —C(S)R_(a), —C(O)NR_(a)R_(b), —C(S)NR_(a)R_(b),—NR_(a)C(O)NR_(b)R_(c), NR_(a)C(S)NR_(b)R_(c), —N(R_(a))SOR_(b),—N(R_(a))SO₂R_(b), —NR_(a)C(O)OR_(b), —NR_(a)R_(b), —NR_(a)C(O)R_(b)—,—NR_(a)C(S)R_(b)—, —SONR_(a)R_(b)—, —SO₂NR_(a)R_(b)—, —OR_(a),—OR_(a)C(O)OR_(b)—, —OC(O)NR_(a)R_(b), OC(O)R_(a), —OC(O)NR_(a)R_(b)—,—R_(a)NR_(b)R_(c), —R_(a)OR_(b)—, —SR_(a), —SOR_(a) and —SO₂R_(a),wherein R_(a), R_(b) and R_(c) is independently selected from the groupconsisting of hydrogen, C₁₋₈ alkyl, C₃₋₈ cycloalkyl, C₅₋₆ aryl, C₇₋₁₅arylalkyl, C₂₋₁₀ heterocyclyl, C₁₋₆ heteroaryl, and C₂₋₁₂heteroarylalkyl with heteroatoms selected from N, O, S;wherein C₇₋₁₂ arylalkoxy, C₁₋₈ alkyl, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₂₋₁₀heterocyclyl, C₃₋₈ cycloalkyl, is optionally substituted with one ormore of the groups selected from hydrogen, C₁₋₆ alkyl, C₅₋₆ aryl, C₁₋₆heteroaryl, C₂₋₁₀ heterocyclyl, oxo (═O), C₃₋₈ cycloalkyl, halogen, OH,amino, and cyano;R₃ is selected from the group consisting of hydrogen, substituted orunsubstituted C₁₋₈ alkyl, and C₅₋₆ aryl;R₂ is selected from the group consisting of —OR₇, aniline, amino C₅₋₆aryl, and amino C₁₋₆ heteroaryl,wherein aniline, amino C₅₋₆ aryl, and amino C₁₋₆ heteroaryl, isoptionally substituted with one or more of the groups selected from C₁₋₈alkyl, halogen, OH, amino, and cyano;R₇ is selected from the group consisting of hydrogen, C₁₋₈ alkyl, C₅₋₆aryl, C₂₋₁₀ heterocyclyl and —COR₈, wherein R₈ is selected from thegroup consisting of C₁₋₈ alkyl, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₃₋₈cycloalkyl, and C₂₋₁₀ heterocyclyl.

In an embodiment of the present invention, there is provided a compoundof Formula I

their analogs, tautomeric forms, stereoisomers, polymorphs, solvates,intermediates, pharmaceutically acceptable salts, metabolites, andprodrugs thereof;whereinAr is selected from the group consisting of substituted or unsubstitutedC₅₋₆aryl, C₁₋₆ heteroaryl, and C₂₋₁₀ heterocyclyl with heteroatomsselected from N, O, S;W represents a bond or CR₄R₅, whereinR₄ and R₅ are independently selected from the group consisting ofhydrogen, substituted or unsubstituted C₁₋₈ alkyl, C₅₋₆ aryl, and C₁₋₆heteroaryl with heteroatoms selected from N, O, S;Y is a bond or is selected from the group consisting of substituted orunsubstituted C₁₋₈ alkenyl, C₁₋₈ alkynyl, C₅₋₆ aryl, C₁₋₆ heteroaryl,C₂₋₁₀ heterocyclyl, C₃₋₈ cycloalkyl, —CO—, and —CO—C₂₋₁₀ heterocyclyl;wherein C₁₋₈ alkyl, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₂₋₁₀ heterocyclyl, C₃₋₈cycloalkyl, is optionally substituted with one or more of the groupsselected from hydrogen, C₁₋₆ alkyl, oxo (═O), C₃₋₈ cycloalkyl, halogen,OH, and cyano;Z represents a bond or is selected from the group consisting of C₁₋₈alkyl, C₁₋₈ alkenyl, C₁₋₈ alkynyl, C₇₋₁₂-alkylaryl, C₇₋₁₂-alkenylaryl,C₇₋₁₅-arylalkenyl, C₂₋₁₂-alkylheteroaryl, —CO—C₇₋₁₂ alkylaryl, —CO—C₇₋₁₂alkenylaryl, —CONR₆—C₁₋₈ alkyl, —NR₆CO—C₁₋₈ alkyl-, —NR₆—C₁₋₈ alkyl,—O—C₁₋₈ alkyl-, —CONR₆—C₅₋₆ aryl-, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₂₋₁₀heterocyclyl, —CO—C₂₋₁₀ heterocyclyl, —NR₆—CO—OC₁₋₈ alkyl, O—CO—NR₆—C₁₋₈alkyl, —NR₆CO—C₅₋₆ aryl-, —NR₆—C₅₋₆ aryl, —NR₆—C₁₋₆ heteroaryl, —C₁₋₈alkyl-O—C₅₋₆ aryl, —O—C₅₋₆ aryl, O—C₁₋₆ heteroaryl, —NR₆—CO—OC₅₋₆ aryl,—CONR₆—C₇₋₁₂ alkylaryl, —CONR₆—C₇₋₁₂ alkenylaryl, —SO₂—C₅₋₆ aryl,—SO₂—C₇₋₁₂ alkylaryl, —NR₆SO₂—C₇₋₁₂ alkylaryl, C₁₋₈ alkyl-CONR₆—C₅₋₆aryl, and O—CO—NR₆—C₅₋₆ aryl;R₆ is selected from the group consisting of hydrogen, C₁₋₈ alkyl, C₁₋₆haloalkyl, C₃₋₈ cycloalkyl, C₅₋₆ aryl, and C₁₋₆ heteroaryl, withheteroatoms selected from N, O, S;R₁ is selected from the group consisting of hydrogen, halogen hydroxy,nitro, cyano, azido, nitroso, oxo (═O), thioxo (═S), —SO₂—, amino,hydrazino, formyl, C₁₋₈ alkyl, C₁₋₈ haloalkyl, C₁₋₈ alkoxy, C₁₋₈haloalkoxy, C₇₋₁₂ arylalkoxy, C₃₋₈ cycloalkyl, C₃₋₈ cycloalkyloxy, C₅₋₆aryl, C₂₋₁₀ heterocyclyl, C₁₋₆ heteroaryl, alkylamino, —COOR_(a),—C(O)R_(b), —C(S)R_(a), —C(O)NR_(a)R_(b), —C(S)NR_(a)R_(b),—NR_(a)C(O)NR_(b)R_(c), NR_(a)C(S)NR_(b)R_(c), —N(R_(a))SOR_(b),—N(R_(a))SO₂R_(b), —NR_(a)C(O)OR_(b), —NR_(a)R_(b), —NR_(a)C(O)R_(b)—,—NR_(a)C(S)R_(b)—, —SONR_(a)R_(b)—, —SO₂NR_(a)R_(b)—, —OR_(a),—OR_(a)C(O)OR_(b)—, —OC(O)NR_(a)R_(b), OC(O)R_(a), —OC(O)NR_(a)R_(b)—,—R_(a)NR_(b)R_(c), —R_(a)OR_(b)—, —SR_(a), —SOR_(a) and —SO₂R_(a),wherein R_(a), R_(b) and R_(c) is independently selected from the groupconsisting of hydrogen, C₁₋₈ alkyl, C₃₋₈ cycloalkyl, C₅₋₆ aryl, C₇₋₁₅arylalkyl, C₂₋₁₀ heterocyclyl, C₁₋₆ heteroaryl, and C₂₋₁₂heteroarylalkyl with heteroatoms selected from N, O, S;wherein C₇₋₁₂ arylalkoxy, C₁₋₈ alkyl, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₂₋₁₀heterocyclyl, C₃₋₈ cycloalkyl, is optionally substituted with one ormore of the groups selected from hydrogen, C₁₋₆ alkyl, C₅₋₆ aryl, C₁₋₆heteroaryl, C₂₋₁₀ heterocyclyl, oxo (═O), C₃₋₈ cycloalkyl, halogen, OH,amino, and cyano;R₃ is selected from the group consisting of hydrogen, substituted orunsubstituted C₁₋₈ alkyl, and C₅₋₆ aryl;R₂ is selected from the group consisting of —OR₇, aniline, amino C₅₋₆aryl, and amino C₁₋₆ heteroaryl,wherein aniline, amino C₅₋₆ aryl, and amino C₁₋₆ heteroaryl, isoptionally substituted with one or more of the groups selected from C₁₋₈alkyl, halogen, OH, amino, and cyano;R₇ is selected from the group consisting of hydrogen, C₁₋₈ alkyl, C₅₋₆aryl, C₂₋₁₀ heterocyclyl and —COR₈, wherein R₈ is selected from thegroup consisting of C₁₋₈ alkyl, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₃₋₈cycloalkyl, and C₂₋₁₀ heterocyclyl.

In an embodiment of the present invention, there is provided a compoundof Formula I

their analogs, tautomeric forms, stereoisomers, polymorphs, solvates,intermediates, pharmaceutically acceptable salts, metabolites, andprodrugs thereof;whereinAr is selected from the group consisting of substituted or unsubstitutedC₅₋₆aryl, C₁₋₆ heteroaryl, and C₂₋₁₀ heterocyclyl with heteroatomsselected from N, O, S;W represents a bond or CR₄R₅, whereinR₄ and R₅ are independently selected from the group consisting ofhydrogen, substituted or unsubstituted C₁₋₈ alkyl, C₅₋₆ aryl, and C₁₋₆heteroaryl with heteroatoms selected from N, O, S;Y is a bond or is selected from the group consisting of substituted orunsubstituted C₁₋₈ alkyl, C₁₋₈ alkenyl, C₁₋₈ alkynyl, C₅₋₆ aryl, C₁₋₆heteroaryl, C₂₋₁₀ heterocyclyl, —CO—, and —CO—C₂₋₁₀ heterocyclyl;wherein C₁₋₈ alkyl, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₂₋₁₀ heterocyclyl, C₃₋₈cycloalkyl, is optionally substituted with one or more of the groupsselected from hydrogen, C₁₋₆ alkyl, oxo (═O), C₃₋₈ cycloalkyl, halogen,OH, and cyano;Z represents a bond or is selected from the group consisting of C₁₋₈alkyl, C₁₋₈ alkenyl, C₁₋₈ alkynyl, C₇₋₁₂-alkylaryl, C₇₋₁₂-alkenylaryl,C₇₋₁₅-arylalkenyl, C₂₋₁₂-alkylheteroaryl, —CO—C₇₋₁₂ alkylaryl, —CO—C₇₋₁₂alkenylaryl, —CONR₆—C₁₋₈ alkyl, —NR₆CO—C₁₋₈ alkyl-, —NR₆—C₁₋₈ alkyl,—O—C₁₋₈ alkyl-, —CONR₆—C₅₋₆ aryl-, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₂₋₁₀heterocyclyl, —CO—C₂₋₁₀ heterocyclyl, —NR₆—CO—OC₁₋₈ alkyl, O—CO—NR₆—C₁₋₈alkyl, —NR₆CO—C₅₋₆ aryl-, —NR₆—C₅₋₆ aryl, —NR₆—C₁₋₆ heteroaryl, —C₁₋₈alkyl-O—C₅₋₆ aryl, —O—C₅₋₆ aryl, O—C₁₋₆ heteroaryl, —NR₆—CO—OC₅₋₆ aryl,—CONR₆—C₇₋₁₂ alkylaryl, —CONR₆—C₇₋₁₂ alkenylaryl, —SO₂—C₅₋₆ aryl,—SO₂—C₇₋₁₂ alkylaryl, —NR₆SO₂—C₇₋₁₂ alkylaryl, C₁₋₈ alkyl-CONR₆—C₅₋₆aryl, and O—CO—NR₆—C₅₋₆ aryl;R₆ is selected from the group consisting of hydrogen, C₁₋₈ alkyl, C₁₋₆haloalkyl, C₃₋₈ cycloalkyl, C₅₋₆ aryl, and C₁₋₆ heteroaryl, withheteroatoms selected from N, O, S;R₁ is selected from the group consisting of hydrogen, halogen hydroxy,nitro, cyano, azido, nitroso, oxo (═O), thioxo (═S), —SO₂—, amino,hydrazino, formyl, C₁₋₈ alkyl, C₁₋₈ haloalkyl, C₁₋₈ alkoxy, C₁₋₈haloalkoxy, C₇₋₁₂ arylalkoxy, C₃₋₈ cycloalkyl, C₃₋₈ cycloalkyloxy, C₅₋₆aryl, C₂₋₁₀ heterocyclyl, C₁₋₆ heteroaryl, alkylamino, —COOR_(a),—C(O)R_(b), —C(S)R_(a), —C(O)NR_(a)R_(b), —C(S)NR_(a)R_(b),—NR_(a)C(O)NR_(b)R_(c), NR_(a)C(S)NR_(b)R_(c), —N(R_(a))SOR_(b),—N(R_(a))SO₂R_(b), —NR_(a)C(O)OR_(b), —NR_(a)R_(b), —NR_(a)C(O)R_(b)—,—NR_(a)C(S)R_(b)—, —SONR_(a)R_(b)—, —SO₂NR_(a)R_(b)—, —OR_(a),—OR_(a)C(O)OR_(b)—, —OC(O)NR_(a)R_(b), OC(O)R_(a), —OC(O)NR_(a)R_(b)—,—R_(a)NR_(b)R_(c), —R_(a)OR_(b)—, —SR_(a), —SOR_(a) and —SO₂R_(a),wherein R_(a), R_(b) and R_(c) is independently selected from the groupconsisting of hydrogen, C₁₋₈ alkyl, C₃₋₈ cycloalkyl, C₅₋₆ aryl, C₇₋₁₅arylalkyl, C₂₋₁₀ heterocyclyl, C₁₋₆ heteroaryl, and C₂₋₁₂heteroarylalkyl with heteroatoms selected from N, O, S;wherein C₇₋₁₂ arylalkoxy, C₁₋₈ alkyl, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₂₋₁₀heterocyclyl, C₃₋₈ cycloalkyl, is optionally substituted with one ormore of the groups selected from hydrogen, C₁₋₆ alkyl, C₅₋₆ aryl, C₁₋₆heteroaryl, C₂₋₁₀ heterocyclyl, oxo (═O), C₃₋₈ cycloalkyl, halogen, OH,amino, and cyano;R₃ is selected from the group consisting of hydrogen, substituted orunsubstituted C₁₋₈ alkyl, and C₅₋₆ aryl;R₂ is selected from the group consisting of —OR₇, aniline, amino C₅₋₆aryl, and amino C₁₋₆ heteroaryl,wherein aniline, amino C₅₋₆ aryl, and amino C₁₋₆ heteroaryl, isoptionally substituted with one or more of the groups selected from C₁₋₈alkyl, halogen, OH, amino, and cyano;R₇ is selected from the group consisting of hydrogen, C₁₋₈ alkyl, C₅₋₆aryl, C₂₋₁₀ heterocyclyl and —COR₈, wherein R₈ is selected from thegroup consisting of C₁₋₈ alkyl, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₃₋₈cycloalkyl, and C₂₋₁₀ heterocyclyl.

In an embodiment of the present invention, there is provided a compoundof Formula I

their analogs, tautomeric forms, stereoisomers, polymorphs, solvates,intermediates, pharmaceutically acceptable salts, metabolites, andprodrugs thereof;whereinAr is selected from the group consisting of substituted or unsubstitutedC₅₋₆aryl, C₁₋₆ heteroaryl, and C₂₋₁₀ heterocyclyl with heteroatomsselected from N, O, S;W represents a bond or CR₄R₅, whereinR₄ and R₅ are independently selected from the group consisting ofhydrogen, substituted or unsubstituted C₁₋₈ alkyl, C₅₋₆ aryl, and C₁₋₆heteroaryl with heteroatoms selected from N, O, S;Y is a bond or is selected from the group consisting of substituted orunsubstituted C₁₋₈ alkyl, C₁₋₈ alkenyl, C₁₋₈ alkynyl, C₅₋₆ aryl, C₂₋₁₀heterocyclyl, C₃₋₈ cycloalkyl, —CO—, and —CO—C₂₋₁₀ heterocyclyl;wherein C₁₋₈ alkyl, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₂₋₁₀ heterocyclyl, C₃₋₈cycloalkyl, is optionally substituted with one or more of the groupsselected from hydrogen, C₁₋₆ alkyl, oxo (═O), C₃₋₈ cycloalkyl, halogen,OH, and cyano;Z represents a bond or is selected from the group consisting of C₁₋₈alkyl, C₁₋₈ alkenyl, C₁₋₈ alkynyl, C₇₋₁₂-alkylaryl, C₇₋₁₂-alkenylaryl,C₇₋₁₅-arylalkenyl, C₂₋₁₂-alkylheteroaryl, —CO—C₇₋₁₂ alkylaryl, —CO—C₇₋₁₂alkenylaryl, —CONR₆—C₁₋₈ alkyl, —NR₆CO—C₁₋₈ alkyl-, —NR₆—C₁₋₈ alkyl,—O—C₁₋₈ alkyl-, —CONR₆—C₅₋₆ aryl-, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₂₋₁₀heterocyclyl, —CO—C₂₋₁₀ heterocyclyl, —NR₆—CO—OC₁₋₈ alkyl, O—CO—NR₆—C₁₋₈alkyl, —NR₆CO—C₅₋₆ aryl-, —NR₆—C₅₋₆ aryl, —NR₆—C₁₋₆ heteroaryl, —C₁₋₈alkyl-O—C₅₋₆ aryl, —O—C₅₋₆ aryl, O—C₁₋₆ heteroaryl, —NR₆—CO—OC₅₋₆ aryl,—CONR₆—C₇₋₁₂ alkylaryl, —CONR₆—C₇₋₁₂ alkenylaryl, —SO₂—C₅₋₆ aryl,—SO₂—C₇₋₁₂ alkylaryl, —NR₆SO₂—C₇₋₁₂ alkylaryl, C₁₋₈ alkyl-CONR₆—C₅₋₆aryl, and O—CO—NR₆—C₅₋₆ aryl;R₆ is selected from the group consisting of hydrogen, C₁₋₈ alkyl, C₁₋₆haloalkyl, C₃₋₈ cycloalkyl, C₅₋₆ aryl, and C₁₋₆ heteroaryl, withheteroatoms selected from N, O, S;R₁ is selected from the group consisting of hydrogen, halogen hydroxy,nitro, cyano, azido, nitroso, oxo (═O), thioxo (═S), —SO₂—, amino,hydrazino, formyl, C₁₋₈ alkyl, C₁₋₈ haloalkyl, C₁₋₈ alkoxy, C₁₋₈haloalkoxy, C₇₋₁₂ arylalkoxy, C₃₋₈ cycloalkyl, C₃₋₈ cycloalkyloxy, C₅₋₆aryl, C₂₋₁₀ heterocyclyl, C₁₋₆ heteroaryl, alkylamino, —COOR_(a),—C(O)R_(b), —C(S)R_(a), —C(O)NR_(a)R_(b), —C(S)NR_(a)R_(b),—NR_(a)C(O)NR_(b)R_(c), NR_(a)C(S)NR_(b)R_(c), —N(R_(a))SOR_(b),—N(R_(a))SO₂R_(b), —NR_(a)C(O)OR_(b), —NR_(a)R_(b), —NR_(a)C(O)R_(b)—,—NR_(a)C(S)R_(b)—, —SONR_(a)R_(b)—, —SO₂NR_(a)R_(b)—, —OR_(a),—OR_(a)C(O)OR_(b)—, —OC(O)NR_(a)R_(b), OC(O)R_(a), —OC(O)NR_(a)R_(b)—,—R_(a)NR_(b)R_(c), —R_(a)OR_(b)—, —SR_(a), —SOR_(a) and —SO₂R_(a),wherein R_(a), R_(b) and R_(c) is independently selected from the groupconsisting of hydrogen, C₁₋₈ alkyl, C₃₋₈ cycloalkyl, C₅₋₆ aryl, C₇₋₁₅arylalkyl, C₂₋₁₀ heterocyclyl, C₁₋₆ heteroaryl, and C₂₋₁₂heteroarylalkyl with heteroatoms selected from N, O, S;wherein C₇₋₁₂ arylalkoxy, C₁₋₈ alkyl, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₂₋₁₀heterocyclyl, C₃₋₈ cycloalkyl, is optionally substituted with one ormore of the groups selected from hydrogen, C₁₋₆ alkyl, C₅₋₆ aryl, C₁₋₆heteroaryl, C₂₋₁₀ heterocyclyl, oxo (═O), C₃₋₈ cycloalkyl, halogen, OH,amino, and cyano;R₃ is selected from the group consisting of hydrogen, substituted orunsubstituted C₁₋₈ alkyl, and C₅₋₆ aryl;R₂ is selected from the group consisting of —OR₇, aniline, amino C₅₋₆aryl, and amino C₁₋₆ heteroaryl,wherein aniline, amino C₅₋₆ aryl, and amino C₁₋₆ heteroaryl, isoptionally substituted with one or more of the groups selected from C₁₋₈alkyl, halogen, OH, amino, and cyano;R₇ is selected from the group consisting of hydrogen, C₁₋₈ alkyl, C₅₋₆aryl, C₂₋₁₀ heterocyclyl and —COR₈, wherein R₈ is selected from thegroup consisting of C₁₋₈ alkyl, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₃₋₈cycloalkyl, and C₂₋₁₀ heterocyclyl.

In an embodiment of the present invention, there is provided a compoundof Formula I

their analogs, tautomeric forms, stereoisomers, polymorphs, solvates,intermediates, pharmaceutically acceptable salts, metabolites, andprodrugs thereof;whereinAr is selected from the group consisting of substituted or unsubstitutedC₅₋₆aryl, C₁₋₆ heteroaryl, and C₂₋₁₀ heterocyclyl with heteroatomsselected from N, O, S;W represents a bond or CR₄R₅, whereinR₄ and R₅ are independently selected from the group consisting ofhydrogen, substituted or unsubstituted C₁₋₈ alkyl, C₅₋₆ aryl, and C₁₋₆heteroaryl with heteroatoms selected from N, O, S;Y is a bond or is selected from the group consisting of substituted orunsubstituted C₁₋₈ alkyl, C₁₋₈ alkenyl, C₁₋₈ alkynyl, C₅₋₆ aryl, C₁₋₆heteroaryl, C₂₋₁₀ heterocyclyl, C₃₋₈ cycloalkyl, and —CO—;wherein C₁₋₈ alkyl, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₂₋₁₀ heterocyclyl, C₃₋₈cycloalkyl, is optionally substituted with one or more of the groupsselected from hydrogen, C₁₋₆ alkyl, oxo (═O), C₃₋₈ cycloalkyl, halogen,OH, and cyano;Z represents a bond or is selected from the group consisting of C₁₋₈alkyl, C₁₋₈ alkenyl, C₁₋₈ alkynyl, C₇₋₁₂-alkylaryl, C₇₋₁₂-alkenylaryl,C₇₋₁₅-arylalkenyl, C₂₋₁₂-alkylheteroaryl, —CO—C₇₋₁₂ alkylaryl, —CO—C₇₋₁₂alkenylaryl, —CONR₆—C₁₋₈ alkyl, —NR₆CO—C₁₋₈ alkyl-, —NR₆—C₁₋₈ alkyl,—O—C₁₋₈ alkyl-, —CONR₆—C₅₋₆ aryl-, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₂₋₁₀heterocyclyl, —CO—C₂₋₁₀ heterocyclyl, —NR₆—CO—OC₁₋₈ alkyl, O—CO—NR₆—C₁₋₈alkyl, —NR₆CO—C₅₋₆ aryl-, —NR₆—C₅₋₆ aryl, —NR₆—C₁₋₆ heteroaryl, —C₁₋₈alkyl-O—C₅₋₆ aryl, —O—C₅₋₆ aryl, O—C₁₋₆ heteroaryl, —NR₆—CO—OC₅₋₆ aryl,—CONR₆—C₇₋₁₂ alkylaryl, —CONR₆—C₇₋₁₂ alkenylaryl, —SO₂—C₅₋₆ aryl,—SO₂—C₇₋₁₂ alkylaryl, —NR₆SO₂—C₇₋₁₂ alkylaryl, C₁₋₈ alkyl-CONR₆—C₅₋₆aryl, and O—CO—NR₆—C₅₋₆ aryl;R₆ is selected from the group consisting of hydrogen, C₁₋₈ alkyl, C₁₋₆haloalkyl, C₃₋₈ cycloalkyl, C₅₋₆ aryl, and C₁₋₆ heteroaryl, withheteroatoms selected from N, O, S;R₁ is selected from the group consisting of hydrogen, halogen hydroxy,nitro, cyano, azido, nitroso, oxo (═O), thioxo (═S), —SO₂—, amino,hydrazino, formyl, C₁₋₈ alkyl, C₁₋₈ haloalkyl, C₁₋₈ alkoxy, C₁₋₈haloalkoxy, C₇₋₁₂ arylalkoxy, C₃₋₈ cycloalkyl, C₃₋₈ cycloalkyloxy, C₅₋₆aryl, C₂₋₁₀ heterocyclyl, C₁₋₆ heteroaryl, alkylamino, —COOR_(a),—C(O)R_(b), —C(S)R_(a), —C(O)NR_(a)R_(b), —C(S)NR_(a)R_(b),—NR_(a)C(O)NR_(b)R_(c), NR_(a)C(S)NR_(b)R_(c), —N(R_(a))SOR_(b),—N(R_(a))SO₂R_(b), —NR_(a)C(O)OR_(b), —NR_(a)R_(b), —NR_(a)C(O)R_(b)—,—NR_(a)C(S)R_(b)—, —SONR_(a)R_(b)—, —SO₂NR_(a)R_(b)—, —OR_(a),—OR_(a)C(O)OR_(b)—, —OC(O)NR_(a)R_(b), OC(O)R_(a), —OC(O)NR_(a)R_(b)—,—R_(a)NR_(b)R_(c), —R_(a)OR_(b)—, —SR_(a), —SOR_(a) and —SO₂R_(a),wherein R_(a), R_(b) and R_(c) is independently selected from the groupconsisting of hydrogen, C₁₋₈ alkyl, C₃₋₈ cycloalkyl, C₅₋₆ aryl, C₇₋₁₅arylalkyl, C₂₋₁₀ heterocyclyl, C₁₋₆ heteroaryl, and C₂₋₁₂heteroarylalkyl with heteroatoms selected from N, O, S;wherein C₇₋₁₂ arylalkoxy, C₁₋₈ alkyl, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₂₋₁₀heterocyclyl, C₃₋₈ cycloalkyl, is optionally substituted with one ormore of the groups selected from hydrogen, C₁₋₆ alkyl, C₅₋₆ aryl, C₁₋₆heteroaryl, C₂₋₁₀ heterocyclyl, oxo (═O), C₃₋₈ cycloalkyl, halogen, OH,amino, and cyano;R₃ is selected from the group consisting of hydrogen, substituted orunsubstituted C₁₋₈ alkyl, and C₅₋₆ aryl;R₂ is selected from the group consisting of —OR₇, aniline, amino C₅₋₆aryl, and amino C₁₋₆ heteroaryl,wherein aniline, amino C₅₋₆ aryl, and amino C₁₋₆ heteroaryl, isoptionally substituted with one or more of the groups selected from C₁₋₈alkyl, halogen, OH, amino, and cyano;R₇ is selected from the group consisting of hydrogen, C₁₋₈ alkyl, C₅₋₆aryl, C₂₋₁₀ heterocyclyl and —COR₈, wherein R₈ is selected from thegroup consisting of C₁₋₈ alkyl, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₃₋₈cycloalkyl, and C₂₋₁₀ heterocyclyl.

In an embodiment of the present invention, there is provided a compoundof Formula I

their analogs, tautomeric forms, stereoisomers, polymorphs, solvates,intermediates, pharmaceutically acceptable salts, metabolites, andprodrugs thereof;whereinAr is selected from the group consisting of substituted or unsubstitutedC₅₋₆aryl, C₁₋₆ heteroaryl, and C₂₋₁₀ heterocyclyl with heteroatomsselected from N, O, S;W represents a bond or CR₄R₅, whereinR₄ and R₅ are independently selected from the group consisting ofhydrogen, substituted or unsubstituted C₁₋₈ alkyl, C₅₋₆ aryl, and C₁₋₆heteroaryl with heteroatoms selected from N, O, S;Y is a bond or is selected from the group consisting of substituted orunsubstituted C₁₋₈ alkyl, C₁₋₈ alkenyl, C₁₋₈ alkynyl, C₅₋₆ aryl, C₁₋₆heteroaryl, C₂₋₁₀ heterocyclyl, C₃₋₈ cycloalkyl, and —CO—C₂₋₁₀heterocyclyl;wherein C₁₋₈ alkyl, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₂₋₁₀ heterocyclyl, C₃₋₈cycloalkyl, is optionally substituted with one or more of the groupsselected from hydrogen, C₁₋₆ alkyl, oxo (═O), C₃₋₈ cycloalkyl, halogen,OH, and cyano;Z represents a bond or is selected from the group consisting of C₁₋₈alkyl, C₁₋₈ alkenyl, C₁₋₈ alkynyl, C₇₋₁₂-alkylaryl, C₇₋₁₂-alkenylaryl,C₇₋₁₅-arylalkenyl, C₂₋₁₂-alkylheteroaryl, —CO—C₇₋₁₂ alkylaryl, —CO—C₇₋₁₂alkenylaryl, —CONR₆—C₁₋₈ alkyl, —NR₆CO—C₁₋₈ alkyl-, —NR₆—C₁₋₈ alkyl,—O—C₁₋₈ alkyl-, —CONR₆—C₅₋₆ aryl-, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₂₋₁₀heterocyclyl, —CO—C₂₋₁₀ heterocyclyl, —NR₆—CO—OC₁₋₈ alkyl, O—CO—NR₆—C₁₋₈alkyl, —NR₆CO—C₅₋₆ aryl-, —NR₆—C₅₋₆ aryl, —NR₆—C₁₋₆ heteroaryl, —C₁₋₈alkyl-O—C₅₋₆ aryl, —O—C₅₋₆ aryl, O—C₁₋₆ heteroaryl, —NR₆—CO—OC₅₋₆ aryl,—CONR₆—C₇₋₁₂ alkylaryl, —CONR₆—C₇₋₁₂ alkenylaryl, —SO₂—C₅₋₆ aryl,—SO₂—C₇₋₁₂ alkylaryl, —NR₆SO₂—C₇₋₁₂ alkylaryl, C₁₋₈ alkyl-CONR₆—C₅₋₆aryl, and O—CO—NR₆—C₅₋₆ aryl;R₆ is selected from the group consisting of hydrogen, C₁₋₈ alkyl, C₁₋₆haloalkyl, C₃₋₈ cycloalkyl, C₅₋₆ aryl, and C₁₋₆ heteroaryl, withheteroatoms selected from N, O, S;R₁ is selected from the group consisting of hydrogen, halogen hydroxy,nitro, cyano, azido, nitroso, oxo (═O), thioxo (═S), —SO₂—, amino,hydrazino, formyl, C₁₋₈ alkyl, C₁₋₈ haloalkyl, C₁₋₈ alkoxy, C₁₋₈haloalkoxy, C₇₋₁₂ arylalkoxy, C₃₋₈ cycloalkyl, C₃₋₈ cycloalkyloxy, C₅₋₆aryl, C₂₋₁₀ heterocyclyl, C₁₋₆ heteroaryl, alkylamino, —COOR_(a),—C(O)R_(b), —C(S)R_(a), —C(O)NR_(a)R_(b), —C(S)NR_(a)R_(b),—NR_(a)C(O)NR_(b)R_(c), NR_(a)C(S)NR_(b)R_(c), —N(R_(a))SOR_(b),—N(R_(a))SO₂R_(b), —NR_(a)C(O)OR_(b), —NR_(a)R_(b), —NR_(a)C(O)R_(b)—,—NR_(a)C(S)R_(b)—, —SONR_(a)R_(b)—, —SO₂NR_(a)R_(b)—, —OR_(a),—OR_(a)C(O)OR_(b)—, —OC(O)NR_(a)R_(b), OC(O)R_(a), —OC(O)NR_(a)R_(b)—,—R_(a)NR_(b)R_(c), —R_(a)OR_(b)—, —SR_(a), —SOR_(a) and —SO₂R_(a),wherein R_(a), R_(b) and R_(c) is independently selected from the groupconsisting of hydrogen, C₁₋₈ alkyl, C₃₋₈ cycloalkyl, C₅₋₆ aryl, C₇₋₁₅arylalkyl, C₂₋₁₀ heterocyclyl, C₁₋₆ heteroaryl, and C₂₋₁₂heteroarylalkyl with heteroatoms selected from N, O, S;wherein C₇₋₁₂ arylalkoxy, C₁₋₈ alkyl, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₂₋₁₀heterocyclyl, C₃₋₈ cycloalkyl, is optionally substituted with one ormore of the groups selected from hydrogen, C₁₋₆ alkyl, C₅₋₆ aryl, C₁₋₆heteroaryl, C₂₋₁₀ heterocyclyl, oxo (═O), C₃₋₈ cycloalkyl, halogen, OH,amino, and cyano;R₃ is selected from the group consisting of hydrogen, substituted orunsubstituted C₁₋₈ alkyl, and C₅₋₆ aryl;R₂ is selected from the group consisting of —OR₇, aniline, amino C₅₋₆aryl, and amino C₁₋₆ heteroaryl,wherein aniline, amino C₅₋₆ aryl, and amino C₁₋₆ heteroaryl, isoptionally substituted with one or more of the groups selected from C₁₋₈alkyl, halogen, OH, amino, and cyano;R₇ is selected from the group consisting of hydrogen, C₁₋₈ alkyl, C₅₋₆aryl, C₂₋₁₀ heterocyclyl and —COR₈, wherein R₈ is selected from thegroup consisting of C₁₋₈ alkyl, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₃₋₈cycloalkyl, and C₂₋₁₀ heterocyclyl.

In an embodiment of the present invention, there is provided a compoundof Formula I

their analogs, tautomeric forms, stereoisomers, polymorphs, solvates,intermediates, pharmaceutically acceptable salts, metabolites, andprodrugs thereof;whereinAr is selected from the group consisting of substituted or unsubstitutedC₅₋₆aryl, C₁₋₆ heteroaryl, and C₂₋₁₀ heterocyclyl with heteroatomsselected from N, O, S;W represents a bond or CR₄R₅, whereinR₄ and R₅ are independently selected from the group consisting ofhydrogen, substituted or unsubstituted C₁₋₈ alkyl, C₅₋₆ aryl, and C₁₋₆heteroaryl with heteroatoms selected from N, O, S;Y is a bond or is selected from the group consisting of substituted orunsubstituted C₁₋₈ alkyl, C₁₋₈ alkenyl, C₁₋₈ alkynyl, C₅₋₆ aryl, C₁₋₆heteroaryl, C₂₋₁₀ heterocyclyl, C₃₋₈ cycloalkyl, —CO—, and —CO—C₂₋₁₀heterocyclyl;wherein C₁₋₈ alkyl, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₂₋₁₀ heterocyclyl, C₃₋₈cycloalkyl, is optionally substituted with one or more of the groupsselected from hydrogen, C₁₋₆ alkyl, oxo (═O), C₃₋₈ cycloalkyl, halogen,OH, and cyano;Z represents a bond or is selected from the group consisting of C₁₋₈alkyl, C₁₋₈ alkenyl, C₁₋₈ alkynyl, C₇₋₁₂-alkylaryl, C₇₋₁₅-arylalkenyl,C₂₋₁₂-alkylheteroaryl, —CO—C₇₋₁₂ alkylaryl, —CO—C₇₋₁₂ alkenylaryl,—CONR₆—C₁₋₈ alkyl, —NR₆CO—C₁₋₈8 alkyl-, —NR₆—C₁₋₈ alkyl, —O—C₁₋₈ alkyl-,—CONR₆—C₅₋₆ aryl-, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₂₋₁₀ heterocyclyl,—CO—C₂₋₁₀ heterocyclyl, —NR₆—CO—OC₁₋₈ alkyl, O—CO—NR₆—C₁₋₈ alkyl,—NR₆CO—C₅₋₆ aryl-, —NR₆—C₅₋₆ aryl, —NR₆—C₁₋₆ heteroaryl, —C₁₋₈alkyl-O—C₅₋₆ aryl, —O—C₅₋₆ aryl, O—C₁₋₆ heteroaryl, —NR₆—CO—OC₅₋₆ aryl,—CONR₆—C₇₋₁₂ alkylaryl, —CONR₆—C₇₋₁₂ alkenylaryl, —SO₂—C₅₋₆ aryl,—SO₂—C₇₋₁₂ alkylaryl, —NR₆SO₂—C₇₋₁₂ alkylaryl, C₁₋₈ alkyl-CONR₆—C₅₋₆aryl, and O—CO—NR₆—C₅₋₆ aryl;R₆ is selected from the group consisting of hydrogen, C₁₋₈ alkyl, C₁₋₆haloalkyl, C₃₋₈ cycloalkyl, C₅₋₆ aryl, and C₁₋₆ heteroaryl, withheteroatoms selected from N, O, S;R₁ is selected from the group consisting of hydrogen, halogen hydroxy,nitro, cyano, azido, nitroso, oxo (═O), thioxo (═S), —SO₂—, amino,hydrazino, formyl, C₁₋₈ alkyl, C₁₋₈ haloalkyl, C₁₋₈ alkoxy, C₁₋₈haloalkoxy, C₇₋₁₂ arylalkoxy, C₃₋₈ cycloalkyl, C₃₋₈ cycloalkyloxy, C₅₋₆aryl, C₂₋₁₀ heterocyclyl, C₁₋₆ heteroaryl, alkylamino, —COOR_(a),—C(O)R_(b), —C(S)R_(a), —C(O)NR_(a)R_(b), —C(S)NR_(a)R_(b),—NR_(a)C(O)NR_(b)R_(c), NR_(a)C(S)NR_(b)R_(c), —N(R_(a))SOR_(b),—N(R_(a))SO₂R_(b), —NR_(a)C(O)OR_(b), —NR_(a)R_(b), —NR_(a)C(O)R_(b)—,—NR_(a)C(S)R_(b)—, —SONR_(a)R_(b)—, —SO₂NR_(a)R_(b)—, —OR_(a),—OR_(a)C(O)OR_(b)—, —OC(O)NR_(a)R_(b), OC(O)R_(a), —OC(O)NR_(a)R_(b)—,—R_(a)NR_(b)R_(c), —R_(a)OR_(b)—, —SR_(a), —SOR_(a) and —SO₂R_(a),wherein R_(a), R_(b) and R_(c) is independently selected from the groupconsisting of hydrogen, C₁₋₈ alkyl, C₃₋₈ cycloalkyl, C₅₋₆ aryl, C₇₋₁₅arylalkyl, C₂₋₁₀ heterocyclyl, C₁₋₆ heteroaryl, and C₂₋₁₂heteroarylalkyl with heteroatoms selected from N, O, S;wherein C₇₋₁₂ arylalkoxy, C₁₋₈ alkyl, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₂₋₁₀heterocyclyl, C₃₋₈ cycloalkyl, is optionally substituted with one ormore of the groups selected from hydrogen, C₁₋₆ alkyl, C₅₋₆ aryl, C₁₋₆heteroaryl, C₂₋₁₀ heterocyclyl, oxo (═O), C₃₋₈ cycloalkyl, halogen, OH,amino, and cyano;R₃ is selected from the group consisting of hydrogen, substituted orunsubstituted C₁₋₈ alkyl, and C₅₋₆ aryl;R₂ is selected from the group consisting of —OR₇, aniline, amino C₅₋₆aryl, and amino C₁₋₆ heteroaryl,wherein aniline, amino C₅₋₆ aryl, and amino C₁₋₆ heteroaryl, isoptionally substituted with one or more of the groups selected from C₁₋₈alkyl, halogen, OH, amino, and cyano;R₇ is selected from the group consisting of hydrogen, C₁₋₈ alkyl, C₅₋₆aryl, C₂₋₁₀ heterocyclyl and —COR₈, wherein R₈ is selected from thegroup consisting of C₁₋₈ alkyl, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₃₋₈cycloalkyl, and C₂₋₁₀ heterocyclyl.

In an embodiment of the present invention, there is provided a compoundof Formula I

their analogs, tautomeric forms, stereoisomers, polymorphs, solvates,intermediates, pharmaceutically acceptable salts, metabolites, andprodrugs thereof;whereinAr is selected from the group consisting of substituted or unsubstitutedC₅₋₆aryl, C₁₋₆ heteroaryl, and C₂₋₁₀ heterocyclyl with heteroatomsselected from N, O, S;W represents a bond or CR₄R₅, whereinR₄ and R₅ are independently selected from the group consisting ofhydrogen, substituted or unsubstituted C₁₋₈ alkyl, C₅₋₆ aryl, and C₁₋₆heteroaryl with heteroatoms selected from N, O, S;Y is a bond or is selected from the group consisting of substituted orunsubstituted C₁₋₈ alkyl, C₁₋₈ alkenyl, C₁₋₈ alkynyl, C₅₋₆ aryl, C₁₋₆heteroaryl, C₂₋₁₀ heterocyclyl, C₃₋₈ cycloalkyl, —CO—, and —CO—C₂₋₁₀heterocyclyl;wherein C₁₋₈ alkyl, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₂₋₁₀ heterocyclyl, C₃₋₈cycloalkyl, is optionally substituted with one or more of the groupsselected from hydrogen, C₁₋₆ alkyl, oxo (═O), C₃₋₈ cycloalkyl, halogen,OH, and cyano;Z represents a bond or is selected from the group consisting of C₁₋₈alkyl, C₁₋₈ alkenyl, C₁₋₈ alkynyl, C₇₋₁₂-alkylaryl, C₇₋₁₂-alkenylaryl,C₇₋₁₅-arylalkenyl, C₂₋₁₂-alkylheteroaryl, —CO—C₇₋₁₂ alkylaryl, —CO—C₇₋₁₂alkenylaryl, —CONR₆—C₁₋₈ alkyl, —NR₆CO—C₁₋₈ alkyl-, —NR₆—C₁₋₈ alkyl,—O—C₁₋₈ alkyl-, —CONR₆—C₅₋₆ aryl-, C₅₋₆ aryl, C₂₋₁₀ heterocyclyl,—CO—C₂₋₁₀ heterocyclyl, —NR₆—CO—OC₁₋₈ alkyl, O—CO—NR₆—C₁₋₈ alkyl,—NR₆CO—C₅₋₆ aryl-, —NR₆—C₅₋₆ aryl, —NR₆—C₁₋₆ heteroaryl, —C₁₋₈alkyl-O—C₅₋₆ aryl, —O—C₅₋₆ aryl, O—C₁₋₆ heteroaryl, —NR₆—CO—OC₅₋₆ aryl,—CONR₆—C₇₋₁₂ alkylaryl, —CONR₆—C₇₋₁₂ alkenylaryl, —SO₂—C₅₋₆ aryl,—SO₂—C₇₋₁₂ alkylaryl, —NR₆SO₂—C₇₋₁₂ alkylaryl, C₁₋₈ alkyl-CONR₆—C₅₋₆aryl, and O—CO—NR₆—C₅₋₆ aryl;R₆ is selected from the group consisting of hydrogen, C₁₋₈ alkyl, C₁₋₆haloalkyl, C₃₋₈ cycloalkyl, C₅₋₆ aryl, and C₁₋₆ heteroaryl, withheteroatoms selected from N, O, S;R₁ is selected from the group consisting of hydrogen, halogen hydroxy,nitro, cyano, azido, nitroso, oxo (═O), thioxo (═S), —SO₂—, amino,hydrazino, formyl, C₁₋₈ alkyl, C₁₋₈ haloalkyl, C₁₋₈ alkoxy, C₁₋₈haloalkoxy, C₇₋₁₂ arylalkoxy, C₃₋₈ cycloalkyl, C₃₋₈ cycloalkyloxy, C₅₋₆aryl, C₂₋₁₀ heterocyclyl, C₁₋₆ heteroaryl, alkylamino, —COOR_(a),—C(O)R_(b), —C(S)R_(a), —C(O)NR_(a)R_(b), —C(S)NR_(a)R_(b),—NR_(a)C(O)NR_(b)R_(c), NR_(a)C(S)NR_(b)R_(c), —N(R_(a))SOR_(b),—N(R_(a))SO₂R_(b), —NR_(a)C(O)OR_(b), —NR_(a)R_(b), —NR_(a)C(O)R_(b)—,—NR_(a)C(S)R_(b)—, —SONR_(a)R_(b)—, —SO₂NR_(a)R_(b)—, —OR_(a),—OR_(a)C(O)OR_(b)—, —OC(O)NR_(a)R_(b), OC(O)R_(a), —OC(O)NR_(a)R_(b)—,—R_(a)NR_(b)R_(c), —R_(a)OR_(b)—, —SR_(a), —SOR_(a) and —SO₂R_(a),wherein R_(a), R_(b) and R_(c) is independently selected from the groupconsisting of hydrogen, C₁₋₈ alkyl, C₃₋₈ cycloalkyl, C₅₋₆ aryl, C₇₋₁₅arylalkyl, C₂₋₁₀ heterocyclyl, C₁₋₆ heteroaryl, and C₂₋₁₂heteroarylalkyl with heteroatoms selected from N, O, S;wherein C₇₋₁₂ arylalkoxy, C₁₋₈ alkyl, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₂₋₁₀heterocyclyl, C₃₋₈ cycloalkyl, is optionally substituted with one ormore of the groups selected from hydrogen, C₁₋₆ alkyl, C₅₋₆ aryl, C₁₋₆heteroaryl, C₂₋₁₀ heterocyclyl, oxo (═O), C₃₋₈ cycloalkyl, halogen, OH,amino, and cyano;R₃ is selected from the group consisting of hydrogen, substituted orunsubstituted C₁₋₈ alkyl, and C₅₋₆ aryl;R₂ is selected from the group consisting of —OR₇, aniline, amino C₅₋₆aryl, and amino C₁₋₆ heteroaryl,wherein aniline, amino C₅₋₆ aryl, and amino C₁₋₆ heteroaryl, isoptionally substituted with one or more of the groups selected from C₁₋₈alkyl, halogen, OH, amino, and cyano;R₇ is selected from the group consisting of hydrogen, C₁₋₈ alkyl, C₅₋₆aryl, C₂₋₁₀ heterocyclyl and —COR₈, wherein R₈ is selected from thegroup consisting of C₁₋₈ alkyl, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₃₋₈cycloalkyl, and C₂₋₁₀ heterocyclyl.

In an embodiment of the present invention, there is provided a compoundof Formula I

their analogs, tautomeric forms, stereoisomers, polymorphs, solvates,intermediates, pharmaceutically acceptable salts, metabolites, andprodrugs thereof;whereinAr is selected from the group consisting of substituted or unsubstitutedC₅₋₆aryl, C₁₋₆ heteroaryl, and C₂₋₁₀ heterocyclyl with heteroatomsselected from N, O, S;W represents a bond or CR₄R₅, whereinR₄ and R₅ are independently selected from the group consisting ofhydrogen, substituted or unsubstituted C₁₋₈ alkyl, C₅₋₆ aryl, and C₁₋₆heteroaryl with heteroatoms selected from N, O, S;Y is a bond or is selected from the group consisting of substituted orunsubstituted C₁₋₈ alkyl, C₁₋₈ alkenyl, C₁₋₈ alkynyl, C₅₋₆ aryl, C₁₋₆heteroaryl, C₂₋₁₀ heterocyclyl, C₃₋₈ cycloalkyl, —CO—, and —CO—C₂₋₁₀heterocyclyl;wherein C₁₋₈ alkyl, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₂₋₁₀ heterocyclyl, C₃₋₈cycloalkyl, is optionally substituted with one or more of the groupsselected from hydrogen, C₁₋₆ alkyl, oxo (═O), C₃₋₈ cycloalkyl, halogen,OH, and cyano;Z represents a bond or is selected from the group consisting of C₁₋₈alkyl, C₁₋₈ alkenyl, C₁₋₈ alkynyl, C₇₋₁₂-alkylaryl, C₇₋₁₂-alkenylaryl,C₇₋₁₅-arylalkenyl, C₂₋₁₂-alkylheteroaryl, —CO—C₇₋₁₂ alkylaryl, —CO—C₇₋₁₂alkenylaryl, —CONR₆—C₁₋₈ alkyl, —NR₆CO—C₁₋₈ alkyl-, —NR₆—C₁₋₈ alkyl,—O—C₁₋₈ alkyl-, —CONR₆—C₅₋₆ aryl-, C₁₋₆ heteroaryl, C₂₋₁₀ heterocyclyl,—CO—C₂₋₁₀ heterocyclyl, —NR₆—CO—OC₁₋₈ alkyl, O—CO—NR₆—C₁₋₈ alkyl,—NR₆CO—C₅₋₆ aryl-, —NR₆—C₅₋₆ aryl, —NR₆—C₁₋₆ heteroaryl, —C₁₋₈alkyl-O—C₅₋₆ aryl, —O—C₅₋₆ aryl, O—C₁₋₆ heteroaryl, —NR₆—CO—OC₅₋₆ aryl,—CONR₆—C₇₋₁₂ alkylaryl, —CONR₆—C₇₋₁₂ alkenylaryl, —SO₂—C₅₋₆ aryl,—SO₂—C₇₋₁₂ alkylaryl, —NR₆SO₂—C₇₋₁₂ alkylaryl, C₁₋₈ alkyl-CONR₆—C₅₋₆aryl, and O—CO—NR₆—C₅₋₆ aryl;R₆ is selected from the group consisting of hydrogen, C₁₋₈ alkyl, C₁₋₆haloalkyl, C₃₋₈ cycloalkyl, C₅₋₆ aryl, and C₁₋₆ heteroaryl, withheteroatoms selected from N, O, S;R₁ is selected from the group consisting of hydrogen, halogen hydroxy,nitro, cyano, azido, nitroso, oxo (═O), thioxo (═S), —SO₂—, amino,hydrazino, formyl, C₁₋₈ alkyl, C₁₋₈ haloalkyl, C₁₋₈ alkoxy, C₁₋₈haloalkoxy, C₇₋₁₂ arylalkoxy, C₃₋₈ cycloalkyl, C₃₋₈ cycloalkyloxy, C₅₋₆aryl, C₂₋₁₀ heterocyclyl, C₁₋₆ heteroaryl, alkylamino, —COOR_(a),—C(O)R_(b), —C(S)R_(a), —C(O)NR_(a)R_(b), —C(S)NR_(a)R_(b),—NR_(a)C(O)NR_(b)R_(c), NR_(a)C(S)NR_(b)R_(c), —N(R_(a))SOR_(b),—N(R_(a))SO₂R_(b), —NR_(a)C(O)OR_(b), —NR_(a)R_(b), —NR_(a)C(O)R_(b)—,—NR_(a)C(S)R_(b)—, —SONR_(a)R_(b)—, —SO₂NR_(a)R_(b)—, —OR_(a),—OR_(a)C(O)OR_(b)—, —OC(O)NR_(a)R_(b), OC(O)R_(a), —OC(O)NR_(a)R_(b)—,—R_(a)NR_(b)R_(c), —R_(a)OR_(b)—, —SR_(a), —SOR_(a) and —SO₂R_(a),wherein R_(a), R_(b) and R_(c) is independently selected from the groupconsisting of hydrogen, C₁₋₈ alkyl, C₃₋₈ cycloalkyl, C₅₋₆ aryl, C₇₋₁₅arylalkyl, C₂₋₁₀ heterocyclyl, C₁₋₆ heteroaryl, and C₂₋₁₂heteroarylalkyl with heteroatoms selected from N, O, S;wherein C₇₋₁₂ arylalkoxy, C₁₋₈ alkyl, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₂₋₁₀heterocyclyl, C₃₋₈ cycloalkyl, is optionally substituted with one ormore of the groups selected from hydrogen, C₁₋₆ alkyl, C₅₋₆ aryl, C₁₋₆heteroaryl, C₂₋₁₀ heterocyclyl, oxo (═O), C₃₋₈ cycloalkyl, halogen, OH,amino, and cyano;R₃ is selected from the group consisting of hydrogen, substituted orunsubstituted C₁₋₈ alkyl, and C₅₋₆ aryl;R₂ is selected from the group consisting of —OR₇, aniline, amino C₅₋₆aryl, and amino C₁₋₆ heteroaryl,wherein aniline, amino C₅₋₆ aryl, and amino C₁₋₆ heteroaryl, isoptionally substituted with one or more of the groups selected from C₁₋₈alkyl, halogen, OH, amino, and cyano;R₇ is selected from the group consisting of hydrogen, C₁₋₈ alkyl, C₅₋₆aryl, C₂₋₁₀ heterocyclyl and —COR₈, wherein R₈ is selected from thegroup consisting of C₁₋₈ alkyl, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₃₋₈cycloalkyl, and C₂₋₁₀ heterocyclyl.

In an embodiment of the present invention, there is provided a compoundof Formula I

their analogs, tautomeric forms, stereoisomers, polymorphs, solvates,intermediates, pharmaceutically acceptable salts, metabolites, andprodrugs thereof;whereinAr is selected from the group consisting of substituted or unsubstitutedC₅₋₆aryl, C₁₋₆ heteroaryl, and C₂₋₁₀ heterocyclyl with heteroatomsselected from N, O, S;W represents a bond or CR₄R₅, whereinR₄ and R₅ are independently selected from the group consisting ofhydrogen, substituted or unsubstituted C₁₋₈ alkyl, C₅₋₆ aryl, and C₁₋₆heteroaryl with heteroatoms selected from N, O, S;Y is a bond or is selected from the group consisting of substituted orunsubstituted C₁₋₈ alkyl, C₁₋₈ alkenyl, C₁₋₈ alkynyl, C₅₋₆ aryl, C₁₋₆heteroaryl, C₂₋₁₀ heterocyclyl, C₃₋₈ cycloalkyl, —CO—, and —CO—C₂₋₁₀heterocyclyl;wherein C₁₋₈ alkyl, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₂₋₁₀ heterocyclyl, C₃₋₈cycloalkyl, is optionally substituted with one or more of the groupsselected from hydrogen, C₁₋₆ alkyl, oxo (═O), C₃₋₈ cycloalkyl, halogen,OH, and cyano;Z is selected from the group consisting of C₁₋₈ alkyl, C₁₋₈ alkenyl,C₁₋₈ alkynyl, C₇₋₁₂-alkylaryl, C₇₋₁₂-alkenylaryl, C₇₋₁₅-arylalkenyl,C₂₋₁₂-alkylheteroaryl, —CO—C₇₋₁₂ alkylaryl, —CO—C₇₋₁₂ alkenylaryl,—CONR₆—C₁₋₈ alkyl, —NR₆CO—C₁₋₈ alkyl-, —NR₆—C₁₋₈ alkyl, —O—C₁₋₈ alkyl-,—CONR₆—C₅₋₆ aryl-, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₂₋₁₀ heterocyclyl,—CO—C₂₋₁₀ heterocyclyl, —NR₆—CO—OC₁₋₈ alkyl, O—CO—NR₆—C₁₋₈ alkyl,—NR₆CO—C₅₋₆ aryl-, —NR₆—C₅₋₆ aryl, —NR₆—C₁₋₆ heteroaryl, —C₁₋₈alkyl-O—C₅₋₆ aryl, —O—C₅₋₆ aryl, O—C₁₋₆ heteroaryl, —NR₆—CO—OC₅₋₆ aryl,—CONR₆—C₇₋₁₂ alkylaryl, —CONR₆—C₇₋₁₂ alkenylaryl, —SO₂—C₅₋₆ aryl,—SO₂—C₇₋₁₂ alkylaryl, —NR₆SO₂—C₇₋₁₂ alkylaryl, C₁₋₈ alkyl-CONR₆—C₅₋₆aryl, and O—CO—NR₆—C₅₋₆ aryl;R₆ is selected from the group consisting of hydrogen, C₁₋₈ alkyl, C₁₋₆haloalkyl, C₃₋₈ cycloalkyl, C₅₋₆ aryl, and C₁₋₆ heteroaryl, withheteroatoms selected from N, O, S;R₁ is selected from the group consisting of hydrogen, halogen hydroxy,nitro, cyano, azido, nitroso, oxo (═O), thioxo (═S), —SO₂—, amino,hydrazino, formyl, C₁₋₈ alkyl, C₁₋₈ haloalkyl, C₁₋₈ alkoxy, C₁₋₈haloalkoxy, C₇₋₁₂ arylalkoxy, C₃₋₈ cycloalkyl, C₃₋₈ cycloalkyloxy, C₅₋₆aryl, C₂₋₁₀ heterocyclyl, C₁₋₆ heteroaryl, alkylamino, —COOR_(a),—C(O)R_(b), —C(S)R_(a), —C(O)NR_(a)R_(b), —C(S)NR_(a)R_(b),—NR_(a)C(O)NR_(b)R_(c), NR_(a)C(S)NR_(b)R_(c), —N(R_(a))SOR_(b),—N(R_(a))SO₂R_(b), —NR_(a)C(O)OR_(b), —NR_(a)R_(b), —NR_(a)C(O)R_(b)—,—NR_(a)C(S)R_(b)—, —SONR_(a)R_(b)—, —SO₂NR_(a)R_(b)—, —OR_(a),—OR_(a)C(O)OR_(b)—, —OC(O)NR_(a)R_(b), OC(O)R_(a), —OC(O)NR_(a)R_(b)—,—R_(a)NR_(b)R_(c), —R_(a)OR_(b)—, —SR_(a), —SOR_(a) and —SO₂R_(a),wherein R_(a), R_(b) and R_(c) is independently selected from the groupconsisting of hydrogen, C₁₋₈ alkyl, C₃₋₈ cycloalkyl, C₅₋₆ aryl, C₇₋₁₅arylalkyl, C₂₋₁₀ heterocyclyl, C₁₋₆ heteroaryl, and C₂₋₁₂heteroarylalkyl with heteroatoms selected from N, O, S;wherein C₇₋₁₂ arylalkoxy, C₁₋₈ alkyl, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₂₋₁₀heterocyclyl, C₃₋₈ cycloalkyl, is optionally substituted with one ormore of the groups selected from hydrogen, C₁₋₆ alkyl, C₅₋₆ aryl, C₁₋₆heteroaryl, C₂₋₁₀ heterocyclyl, oxo (═O), C₃₋₈ cycloalkyl, halogen, OH,amino, and cyano;R₃ is selected from the group consisting of hydrogen, substituted orunsubstituted C₁₋₈ alkyl, and C₅₋₆ aryl;R₂ is selected from the group consisting of —OR₇, aniline, amino C₅₋₆aryl, and amino C₁₋₆ heteroaryl,wherein aniline, amino C₅₋₆ aryl, and amino C₁₋₆ heteroaryl, isoptionally substituted with one or more of the groups selected from C₁₋₈alkyl, halogen, OH, amino, and cyano;R₇ is selected from the group consisting of hydrogen, C₁₋₈ alkyl, C₅₋₆aryl, C₂₋₁₀ heterocyclyl and —COR₈, wherein R₈ is selected from thegroup consisting of C₁₋₈ alkyl, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₃₋₈cycloalkyl, and C₂₋₁₀ heterocyclyl.

In an embodiment of the present invention, there is provided a compoundof Formula I

their analogs, tautomeric forms, stereoisomers, polymorphs, solvates,intermediates, pharmaceutically acceptable salts, metabolites, andprodrugs thereof;whereinAr is selected from the group consisting of substituted or unsubstitutedC₅₋₆aryl, C₁₋₆ heteroaryl, and C₂₋₁₀ heterocyclyl with heteroatomsselected from N, O, S;W represents a bond or CR₄R₅, whereinR₄ and R₅ are independently selected from the group consisting ofhydrogen, substituted or unsubstituted C₁₋₈ alkyl, C₅₋₆ aryl, and C₁₋₆heteroaryl with heteroatoms selected from N, O, S;Y is a bond or is selected from the group consisting of substituted orunsubstituted C₁₋₈ alkyl, C₁₋₈ alkenyl, C₁₋₈ alkynyl, C₅₋₆ aryl, C₁₋₆heteroaryl, C₂₋₁₀ heterocyclyl, C₃₋₈ cycloalkyl, —CO—, and —CO—C₂₋₁₀heterocyclyl;wherein C₁₋₈ alkyl, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₂₋₁₀ heterocyclyl, C₃₋₈cycloalkyl, is optionally substituted with one or more of the groupsselected from hydrogen, C₁₋₆ alkyl, oxo (═O), C₃₋₈ cycloalkyl, halogen,OH, and cyano;Z represents a bond or is selected from the group consisting of C₁₋₈alkyl, C₁₋₈ alkynyl, C₇₋₁₂-alkylaryl, C₇₋₁₂-alkenylaryl,C₇₋₁₅-arylalkenyl, C₂₋₁₂-alkylheteroaryl, —CO—C₇₋₁₂ alkylaryl, —CO—C₇₋₁₂alkenylaryl, —CONR₆—C₁₋₈ alkyl, —NR₆CO—C₁₋₈ alkyl-, —NR₆—C₁₋₈alkyl,—O—C₁₋₈ alkyl-, —CONR₆—C₅₋₆ aryl-, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₂₋₁₀heterocyclyl, —CO—C₂₋₁₀ heterocyclyl, —NR₆—CO—OC₁₋₈ alkyl, O—CO—NR₆—C₁₋₈alkyl, —NR₆CO—C₅₋₆ aryl-, —NR₆—C₅₋₆ aryl, —NR₆—C₁₋₆ heteroaryl, —C₁₋₈alkyl-O—C₅₋₆ aryl, —O—C₅₋₆ aryl, O—C₁₋₆ heteroaryl, —NR₆—CO—OC₅₋₆ aryl,—CONR₆—C₇₋₁₂ alkylaryl, —CONR₆—C₇₋₁₂ alkenylaryl, —SO₂—C₅₋₆ aryl,—SO₂—C₇₋₁₂ alkylaryl, —NR₆SO₂—C₇₋₁₂ alkylaryl, C₁₋₈ alkyl-CONR₆—C₅₋₆aryl, and O—CO—NR₆—C₅₋₆ aryl;R₆ is selected from the group consisting of hydrogen, C₁₋₈ alkyl, C₁₋₆haloalkyl, C₃₋₈ cycloalkyl, C₅₋₆ aryl, and C₁₋₆ heteroaryl, withheteroatoms selected from N, O, S;R₁ is selected from the group consisting of hydrogen, halogen hydroxy,nitro, cyano, azido, nitroso, oxo (═O), thioxo (═S), —SO₂—, amino,hydrazino, formyl, C₁₋₈ alkyl, C₁₋₈ haloalkyl, C₁₋₈ alkoxy, C₁₋₈haloalkoxy, C₇₋₁₂ arylalkoxy, C₃₋₈ cycloalkyl, C₃₋₈ cycloalkyloxy, C₅₋₆aryl, C₂₋₁₀ heterocyclyl, C₁₋₆ heteroaryl, alkylamino, —COOR_(a),—C(O)R_(b), —C(S)R_(a), —C(O)NR_(a)R_(b), —C(S)NR_(a)R_(b),—NR_(a)C(O)NR_(b)R_(c), NR_(a)C(S)NR_(b)R_(c), —N(R_(a))SOR_(b),—N(R_(a))SO₂R_(b), —NR_(a)C(O)OR_(b), —NR_(a)R_(b), —NR_(a)C(O)R_(b)—,—NR_(a)C(S)R_(b)—, —SONR_(a)R_(b)—, —SO₂NR_(a)R_(b)—, —OR_(a),—OR_(a)C(O)OR_(b)—, —OC(O)NR_(a)R_(b), OC(O)R_(a), —OC(O)NR_(a)R_(b)—,—R_(a)NR_(b)R_(c), —R_(a)OR_(b)—, —SR_(a), —SOR_(a) and —SO₂R_(a),wherein R_(a), R_(b) and R_(c) is independently selected from the groupconsisting of hydrogen, C₁₋₈ alkyl, C₃₋₈ cycloalkyl, C₅₋₆ aryl, C₇₋₁₅arylalkyl, C₂₋₁₀ heterocyclyl, C₁₋₆ heteroaryl, and C₂₋₁₂heteroarylalkyl with heteroatoms selected from N, O, S;wherein C₇₋₁₂ arylalkoxy, C₁₋₈ alkyl, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₂₋₁₀heterocyclyl, C₃₋₈ cycloalkyl, is optionally substituted with one ormore of the groups selected from hydrogen, C₁₋₆ alkyl, C₅₋₆ aryl, C₁₋₆heteroaryl, C₂₋₁₀ heterocyclyl, oxo (═O), C₃₋₈ cycloalkyl, halogen, OH,amino, and cyano;R₃ is selected from the group consisting of hydrogen, substituted orunsubstituted C₁₋₈ alkyl, and C₅₋₆ aryl;R₂ is selected from the group consisting of —OR₇, aniline, amino C₅₋₆aryl, and amino C₁₋₆ heteroaryl,wherein aniline, amino C₅₋₆ aryl, and amino C₁₋₆ heteroaryl, isoptionally substituted with one or more of the groups selected from C₁₋₈alkyl, halogen, OH, amino, and cyano;R₇ is selected from the group consisting of hydrogen, C₁₋₈ alkyl, C₅₋₆aryl, C₂₋₁₀ heterocyclyl and —COR₈, wherein R₈ is selected from thegroup consisting of C₁₋₈ alkyl, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₃₋₈cycloalkyl, and C₂₋₁₀ heterocyclyl.

In an embodiment of the present invention, there is provided a compoundof Formula I

their analogs, tautomeric forms, stereoisomers, polymorphs, solvates,intermediates, pharmaceutically acceptable salts, metabolites, andprodrugs thereof;whereinAr is selected from the group consisting of substituted or unsubstitutedC₅₋₆aryl, C₁₋₆ heteroaryl, and C₂₋₁₀ heterocyclyl with heteroatomsselected from N, O, S;W represents a bond or CR₄R₅, whereinR₄ and R₅ are independently selected from the group consisting ofhydrogen, substituted or unsubstituted C₁₋₈ alkyl, C₅₋₆ aryl, and C₁₋₆heteroaryl with heteroatoms selected from N, O, S;Y is a bond or is selected from the group consisting of substituted orunsubstituted C₁₋₈ alkyl, C₁₋₈ alkenyl, C₁₋₈ alkynyl, C₅₋₆ aryl, C₁₋₆heteroaryl, C₂₋₁₀ heterocyclyl, C₃₋₈ cycloalkyl, —CO—, and —CO—C₂₋₁₀heterocyclyl;wherein C₁₋₈ alkyl, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₂₋₁₀ heterocyclyl, C₃₋₈cycloalkyl, is optionally substituted with one or more of the groupsselected from hydrogen, C₁₋₆ alkyl, oxo (═O), C₃₋₈ cycloalkyl, halogen,OH, and cyano;Z represents a bond or is selected from the group consisting of C₁₋₈alkyl, C₁₋₈ alkenyl, C₁₋₈ alkynyl, C₇₋₁₂-alkylaryl, C₇₋₁₂-alkenylaryl,C₇₋₁₅-arylalkenyl, C₂₋₁₂-alkylheteroaryl, —CO—C₇₋₁₂ alkylaryl, —CO—C₇₋₁₂alkenylaryl, —NR₆CO—C₁₋₈ alkyl-, —NR₆—C₁₋₈ alkyl, —O—C₁₋₈ alkyl-,—CONR₆—C₅₋₆ aryl-, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₂₋₁₀ heterocyclyl,—CO—C₂₋₁₀ heterocyclyl, —NR₆—CO—OC₁₋₈ alkyl, O—CO—NR₆—C₁₋₈ alkyl,—NR₆CO—C₅₋₆ aryl-, —NR₆—C₅₋₆ aryl, —NR₆—C₁₋₆ heteroaryl, —C₁₋₈alkyl-O—C₅₋₆ aryl, —O—C₅₋₆ aryl, O—C₁₋₆ heteroaryl, —NR₆—CO—OC₅₋₆ aryl,—CONR₆—C₇₋₁₂ alkylaryl, —CONR₆—C₇₋₁₂ alkenylaryl, —SO₂—C₅₋₆ aryl,—SO₂—C₇₋₁₂ alkylaryl, —NR₆SO₂—C₇₋₁₂ alkylaryl, C₁₋₈ alkyl-CONR₆—C₅₋₆aryl, and O—CO—NR₆—C₅₋₆ aryl;R₆ is selected from the group consisting of hydrogen, C₁₋₈ alkyl, C₁₋₆haloalkyl, C₃₋₈ cycloalkyl, C₅₋₆ aryl, and C₁₋₆ heteroaryl, withheteroatoms selected from N, O, S;R₁ is selected from the group consisting of hydrogen, halogen hydroxy,nitro, cyano, azido, nitroso, oxo (═O), thioxo (═S), —SO₂—, amino,hydrazino, formyl, C₁₋₈ alkyl, C₁₋₈ haloalkyl, C₁₋₈ alkoxy, C₁₋₈haloalkoxy, C₇₋₁₂ arylalkoxy, C₃₋₈ cycloalkyl, C₃₋₈ cycloalkyloxy, C₅₋₆aryl, C₂₋₁₀ heterocyclyl, C₁₋₆ heteroaryl, alkylamino, —COOR_(a),—C(O)R_(b), —C(S)R_(a), —C(O)NR_(a)R_(b), —C(S)NR_(a)R_(b),—NR_(a)C(O)NR_(b)R_(c), NR_(a)C(S)NR_(b)R_(c), —N(R_(a))SOR_(b),—N(R_(a))SO₂R_(b), —NR_(a)C(O)OR_(b), —NR_(a)R_(b), —NR_(a)C(O)R_(b)—,—NR_(a)C(S)R_(b)—, —SONR_(a)R_(b)—, —SO₂NR_(a)R_(b)—, —OR_(a),—OR_(a)C(O)OR_(b)—, —OC(O)NR_(a)R_(b), OC(O)R_(a), —OC(O)NR_(a)R_(b)—,—R_(a)NR_(b)R_(c), —R_(a)OR_(b)—, —SR_(a), —SOR_(a) and —SO₂R_(a),wherein R_(a), R_(b) and R_(c) is independently selected from the groupconsisting of hydrogen, C₁₋₈ alkyl, C₃₋₈ cycloalkyl, C₅₋₆ aryl, C₇₋₁₅arylalkyl, C₂₋₁₀ heterocyclyl, C₁₋₆ heteroaryl, and C₂₋₁₂heteroarylalkyl with heteroatoms selected from N, O, S;wherein C₇₋₁₂ arylalkoxy, C₁₋₈ alkyl, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₂₋₁₀heterocyclyl, C₃₋₈ cycloalkyl, is optionally substituted with one ormore of the groups selected from hydrogen, C₁₋₆ alkyl, C₅₋₆ aryl, C₁₋₆heteroaryl, C₂₋₁₀ heterocyclyl, oxo (═O), C₃₋₈ cycloalkyl, halogen, OH,amino, and cyano;R₃ is selected from the group consisting of hydrogen, substituted orunsubstituted C₁₋₈ alkyl, and C₅₋₆ aryl;R₂ is selected from the group consisting of —OR₇, aniline, amino C₅₋₆aryl, and amino C₁₋₆ heteroaryl,wherein aniline, amino C₅₋₆ aryl, and amino C₁₋₆ heteroaryl, isoptionally substituted with one or more of the groups selected from C₁₋₈alkyl, halogen, OH, amino, and cyano;R₇ is selected from the group consisting of hydrogen, C₁₋₈ alkyl, C₅₋₆aryl, C₂₋₁₀ heterocyclyl and —COR₈, wherein R₈ is selected from thegroup consisting of C₁₋₈ alkyl, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₃₋₈cycloalkyl, and C₂₋₁₀ heterocyclyl.

In an embodiment of the present invention, there is provided a compoundof Formula I

their analogs, tautomeric forms, stereoisomers, polymorphs, solvates,intermediates, pharmaceutically acceptable salts, metabolites, andprodrugs thereof;whereinAr is selected from the group consisting of substituted or unsubstitutedC₅₋₆aryl, C₁₋₆ heteroaryl, and C₂₋₁₀ heterocyclyl with heteroatomsselected from N, O, S;W represents a bond or CR₄R₅, whereinR₄ and R₅ are independently selected from the group consisting ofhydrogen, substituted or unsubstituted C₁₋₈ alkyl, C₅₋₆ aryl, and C₁₋₆heteroaryl with heteroatoms selected from N, O, S;Y is a bond or is selected from the group consisting of substituted orunsubstituted C₁₋₈ alkyl, C₁₋₈ alkenyl, C₁₋₈ alkynyl, C₅₋₆ aryl, C₁₋₆heteroaryl, C₂₋₁₀ heterocyclyl, C₃₋₈ cycloalkyl, —CO—, and —CO—C₂₋₁₀heterocyclyl;wherein C₁₋₈ alkyl, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₂₋₁₀ heterocyclyl, C₃₋₈cycloalkyl, is optionally substituted with one or more of the groupsselected from hydrogen, C₁₋₆ alkyl, oxo (═O), C₃₋₈ cycloalkyl, halogen,OH, and cyano;Z represents a bond or is selected from the group consisting of C₁₋₈alkyl, C₁₋₈ alkenyl, C₁₋₈ alkynyl, C₇₋₁₂-alkenylaryl, C₇₋₁₅-arylalkenyl,C₂₋₁₂-alkylheteroaryl, —CO—C₇₋₁₂ alkylaryl, —CO—C₇₋₁₂ alkenylaryl,—CONR₆—C₁₋₈ alkyl, —NR₆CO—C₁₋₈ alkyl-, —NR₆—C₁₋₈ alkyl, —O—C₁₋₈ alkyl-,—CONR₆—C₅₋₆ aryl-, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₂₋₁₀ heterocyclyl,—CO—C₂₋₁₀ heterocyclyl, —NR₆—CO—OC₁₋₈ alkyl, O—CO—NR₆—C₁₋₈ alkyl,—NR₆CO—C₅₋₆ aryl-, —NR₆—C₅₋₆ aryl, —NR₆—C₁₋₆ heteroaryl, —C₁₋₈alkyl-O—C₅₋₆ aryl, —O—C₅₋₆ aryl, O—C₁₋₆ heteroaryl, —NR₆—CO—OC₅₋₆ aryl,—CONR₆—C₇₋₁₂ alkylaryl, —CONR₆—C₇₋₁₂ alkenylaryl, —SO₂—C₅₋₆ aryl,—SO₂—C₇₋₁₂ alkylaryl, —NR₆SO₂—C₇₋₁₂ alkylaryl, C₁₋₈ alkyl-CONR₆—C₅₋₆aryl, and O—CO—NR₆—C₅₋₆ aryl;R₆ is selected from the group consisting of hydrogen, C₁₋₈ alkyl, C₁₋₆haloalkyl, C₃₋₈ cycloalkyl, C₅₋₆ aryl, and C₁₋₆ heteroaryl, withheteroatoms selected from N, O, S;R₁ is selected from the group consisting of hydrogen, halogen hydroxy,nitro, cyano, azido, nitroso, oxo (═O), thioxo (═S), —SO₂—, amino,hydrazino, formyl, C₁₋₈ alkyl, C₁₋₈ haloalkyl, C₁₋₈ alkoxy, C₁₋₈haloalkoxy, C₇₋₁₂ arylalkoxy, C₃₋₈ cycloalkyl, C₃₋₈ cycloalkyloxy, C₅₋₆aryl, C₂₋₁₀ heterocyclyl, C₁₋₆ heteroaryl, alkylamino, —COOR_(a),—C(O)R_(b), —C(S)R_(a), —C(O)NR_(a)R_(b), —C(S)NR_(a)R_(b),—NR_(a)C(O)NR_(b)R_(c), NR_(a)C(S)NR_(b)R_(c), —N(R_(a))SOR_(b),—N(R_(a))SO₂R_(b), —NR_(a)C(O)OR_(b), —NR_(a)R_(b), —NR_(a)C(O)R_(b)—,—NR_(a)C(S)R_(b)—, —SONR_(a)R_(b)—, —SO₂NR_(a)R_(b)—, —OR_(a),—OR_(a)C(O)OR_(b)—, —OC(O)NR_(a)R_(b), OC(O)R_(a), —OC(O)NR_(a)R_(b)—,—R_(a)NR_(b)R_(c), —R_(a)OR_(b)—, —SR_(a), —SOR_(a) and —SO₂R_(a),wherein R_(a), R_(b) and R_(c) is independently selected from the groupconsisting of hydrogen, C₁₋₈ alkyl, C₃₋₈ cycloalkyl, C₅₋₆ aryl, C₇₋₁₅arylalkyl, C₂₋₁₀ heterocyclyl, C₁₋₆ heteroaryl, and C₂₋₁₂heteroarylalkyl with heteroatoms selected from N, O, S;wherein C₇₋₁₂ arylalkoxy, C₁₋₈ alkyl, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₂₋₁₀heterocyclyl, C₃₋₈ cycloalkyl, is optionally substituted with one ormore of the groups selected from hydrogen, C₁₋₆ alkyl, C₅₋₆ aryl, C₁₋₆heteroaryl, C₂₋₁₀ heterocyclyl, oxo (═O), C₃₋₈ cycloalkyl, halogen, OH,amino, and cyano;R₃ is selected from the group consisting of hydrogen, substituted orunsubstituted C₁₋₈ alkyl, and C₅₋₆ aryl;R₂ is selected from the group consisting of —OR₇, aniline, amino C₅₋₆aryl, and amino C₁₋₆ heteroaryl,wherein aniline, amino C₅₋₆ aryl, and amino C₁₋₆ heteroaryl, isoptionally substituted with one or more of the groups selected from C₁₋₈alkyl, halogen, OH, amino, and cyano;R₇ is selected from the group consisting of hydrogen, C₁₋₈ alkyl, C₅₋₆aryl, C₂₋₁₀ heterocyclyl and —COR₈, wherein R₈ is selected from thegroup consisting of C₁₋₈ alkyl, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₃₋₈cycloalkyl, and C₂₋₁₀ heterocyclyl.

In an embodiment of the present invention, there is provided a compoundof Formula I

their analogs, tautomeric forms, stereoisomers, polymorphs, solvates,intermediates, pharmaceutically acceptable salts, metabolites, andprodrugs thereof;whereinAr is selected from the group consisting of substituted or unsubstitutedC₅₋₆aryl, C₁₋₆ heteroaryl, and C₂₋₁₀ heterocyclyl with heteroatomsselected from N, O, S;W represents a bond or CR₄R₅, whereinR₄ and R₅ are independently selected from the group consisting ofhydrogen, substituted or unsubstituted C₁₋₈ alkyl, C₅₋₆ aryl, and C₁₋₆heteroaryl with heteroatoms selected from N, O, S;Y is a bond or is selected from the group consisting of substituted orunsubstituted C₁₋₈ alkyl, C₁₋₈ alkenyl, C₁₋₈ alkynyl, C₅₋₆ aryl, C₁₋₆heteroaryl, C₂₋₁₀ heterocyclyl, C₃₋₈ cycloalkyl, —CO—, and —CO—C₂₋₁₀heterocyclyl;wherein C₁₋₈ alkyl, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₂₋₁₀ heterocyclyl, C₃₋₈cycloalkyl, is optionally substituted with one or more of the groupsselected from hydrogen, C₁₋₆ alkyl, oxo (═O), C₃₋₈ cycloalkyl, halogen,OH, and cyano;Z represents a bond or is selected from the group consisting of C₁₋₈alkyl, C₁₋₈ alkenyl, C₁₋₈ alkynyl, C₇₋₁₂-alkylaryl, C₇₋₁₂-alkenylaryl,C₇₋₁₅-arylalkenyl, —CO—C₇₋₁₂ alkylaryl, —CO—C₇₋₁₂ alkenylaryl,—CONR₆—C₁₋₈ alkyl, —NR₆CO—C₁₋₈ alkyl-, —NR₆—C₁₋₈ alkyl, —O—C₁₋₈ alkyl-,—CONR₆—C₅₋₆ aryl-, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₂₋₁₀ heterocyclyl,—CO—C₂₋₁₀ heterocyclyl, —NR₆—CO—OC₁₋₈ alkyl, O—CO—NR₆—C₁₋₈ alkyl,—NR₆CO—C₅₋₆ aryl-, —NR₆—C₅₋₆ aryl, —NR₆—C₁₋₆ heteroaryl, —C₁₋₈alkyl-O—C₅₋₆ aryl, —O—C₅₋₆ aryl, O—C₁₋₆ heteroaryl, —NR₆—CO—OC₅₋₆ aryl,—CONR₆—C₇₋₁₂ alkylaryl, —CONR₆—C₇₋₁₂ alkenylaryl, —SO₂—C₅₋₆ aryl,—SO₂—C₇₋₁₂ alkylaryl, —NR₆SO₂—C₇₋₁₂ alkylaryl, C₁₋₈ alkyl-CONR₆—C₅₋₆aryl, and O—CO—NR₆—C₅₋₆ aryl;R₆ is selected from the group consisting of hydrogen, C₁₋₈ alkyl, C₁₋₆haloalkyl, C₃₋₈ cycloalkyl, C₅₋₆ aryl, and C₁₋₆ heteroaryl, withheteroatoms selected from N, O, S;R₁ is selected from the group consisting of hydrogen, halogen hydroxy,nitro, cyano, azido, nitroso, oxo (═O), thioxo (═S), —SO₂—, amino,hydrazino, formyl, C₁₋₈ alkyl, C₁₋₈ haloalkyl, C₁₋₈ alkoxy, C₁₋₈haloalkoxy, C₇₋₁₂ arylalkoxy, C₃₋₈ cycloalkyl, C₃₋₈ cycloalkyloxy, C₅₋₆aryl, C₂₋₁₀ heterocyclyl, C₁₋₆ heteroaryl, alkylamino, —COOR_(a),—C(O)R_(b), —C(S)R_(a), —C(O)NR_(a)R_(b), —C(S)NR_(a)R_(b),—NR_(a)C(O)NR_(b)R_(c), NR_(a)C(S)NR_(b)R_(c), —N(R_(a))SOR_(b),—N(R_(a))SO₂R_(b), —NR_(a)C(O)OR_(b), —NR_(a)R_(b), —NR_(a)C(O)R_(b)—,—NR_(a)C(S)R_(b)—, —SONR_(a)R_(b)—, —SO₂NR_(a)R_(b)—, —OR_(a),—OR_(a)C(O)OR_(b)—, —OC(O)NR_(a)R_(b), OC(O)R_(a), —OC(O)NR_(a)R_(b)—,—R_(a)NR_(b)R_(c), —R_(a)OR_(b)—, —SR_(a), —SOR_(a) and —SO₂R_(a),wherein R_(a), R_(b) and R_(c) is independently selected from the groupconsisting of hydrogen, C₁₋₈ alkyl, C₃₋₈ cycloalkyl, C₅₋₆ aryl, C₇₋₁₅arylalkyl, C₂₋₁₀ heterocyclyl, C₁₋₆ heteroaryl, and C₂₋₁₂heteroarylalkyl with heteroatoms selected from N, O, S;wherein C₇₋₁₂ arylalkoxy, C₁₋₈ alkyl, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₂₋₁₀heterocyclyl, C₃₋₈ cycloalkyl, is optionally substituted with one ormore of the groups selected from hydrogen, C₁₋₆ alkyl, C₅₋₆ aryl, C₁₋₆heteroaryl, C₂₋₁₀ heterocyclyl, oxo (═O), C₃₋₈ cycloalkyl, halogen, OH,amino, and cyano;R₃ is selected from the group consisting of hydrogen, substituted orunsubstituted C₁₋₈ alkyl, and C₅₋₆ aryl;R₂ is selected from the group consisting of —OR₇, aniline, amino C₅₋₆aryl, and amino C₁₋₆ heteroaryl,wherein aniline, amino C₅₋₆ aryl, and amino C₁₋₆ heteroaryl, isoptionally substituted with one or more of the groups selected from C₁₋₈alkyl, halogen, OH, amino, and cyano;R₇ is selected from the group consisting of hydrogen, C₁₋₈ alkyl, C₅₋₆aryl, C₂₋₁₀ heterocyclyl and —COR₈, wherein R₈ is selected from thegroup consisting of C₁₋₈ alkyl, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₃₋₈cycloalkyl, and C₂₋₁₀ heterocyclyl.

In an embodiment of the present invention, there is provided a compoundof Formula I

their analogs, tautomeric forms, stereoisomers, polymorphs, solvates,intermediates, pharmaceutically acceptable salts, metabolites, andprodrugs thereof;whereinAr is selected from the group consisting of substituted or unsubstitutedC₅₋₆aryl, C₁₋₆ heteroaryl, and C₂₋₁₀ heterocyclyl with heteroatomsselected from N, O, S;W represents a bond or CR₄R₅, whereinR₄ and R₅ are independently selected from the group consisting ofhydrogen, substituted or unsubstituted C₁₋₈ alkyl, C₅₋₆ aryl, and C₁₋₆heteroaryl with heteroatoms selected from N, O, S;Y is a bond or is selected from the group consisting of substituted orunsubstituted C₁₋₈ alkyl, C₁₋₈ alkenyl, C₁₋₈ alkynyl, C₅₋₆ aryl, C₁₋₆heteroaryl, C₂₋₁₀ heterocyclyl, C₃₋₈ cycloalkyl, —CO—, and —CO—C₂₋₁₀heterocyclyl;wherein C₁₋₈ alkyl, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₂₋₁₀ heterocyclyl, C₃₋₈cycloalkyl, is optionally substituted with one or more of the groupsselected from hydrogen, C₁₋₆ alkyl, oxo (═O), C₃₋₈ cycloalkyl, halogen,OH, and cyano;Z represents a bond or is selected from the group consisting of C₁₋₈alkyl, C₁₋₈ alkenyl, C₁₋₈ alkynyl, C₇₋₁₂-alkylaryl, C₇₋₁₂-alkenylaryl,C₇₋₁₅-arylalkenyl, C₂₋₁₂-alkylheteroaryl, —CO—C₇₋₁₂ alkenylaryl,—CONR₆—C₁₋₈ alkyl, —NR₆CO—C₁₋₈ alkyl-, —NR₆—C₁₋₈ alkyl, —O—C₁₋₈ alkyl-,—CONR₆—C₅₋₆ aryl-, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₂₋₁₀ heterocyclyl,—CO—C₂₋₁₀ heterocyclyl, —NR₆—CO—OC₁₋₈ alkyl, O—CO—NR₆—C₁₋₈ alkyl,—NR₆CO—C₅₋₆ aryl-, —NR₆—C₅₋₆ aryl, —NR₆—C₁₋₆ heteroaryl, —C₁₋₈alkyl-O—C₅₋₆ aryl, —O—C₅₋₆ aryl, O—C₁₋₆ heteroaryl, —NR₆—CO—OC₅₋₆ aryl,—CONR₆—C₇₋₁₂ alkylaryl, —CONR₆—C₇₋₁₂ alkenylaryl, —SO₂—C₅₋₆ aryl,—SO₂—C₇₋₁₂ alkylaryl, —NR₆SO₂—C₇₋₁₂ alkylaryl, C₁₋₈ alkyl-CONR₆—C₅₋₆aryl, and O—CO—NR₆—C₅₋₆ aryl;R₆ is selected from the group consisting of hydrogen, C₁₋₈ alkyl, C₁₋₆haloalkyl, C₃₋₈ cycloalkyl, C₅₋₆ aryl, and C₁₋₆ heteroaryl, withheteroatoms selected from N, O, S;R₁ is selected from the group consisting of hydrogen, halogen hydroxy,nitro, cyano, azido, nitroso, oxo (═O), thioxo (═S), —SO₂—, amino,hydrazino, formyl, C₁₋₈ alkyl, C₁₋₈ haloalkyl, C₁₋₈ alkoxy, C₁₋₈haloalkoxy, C₇₋₁₂ arylalkoxy, C₃₋₈ cycloalkyl, C₃₋₈ cycloalkyloxy, C₅₋₆aryl, C₂₋₁₀ heterocyclyl, C₁₋₆ heteroaryl, alkylamino, —COOR_(a),—C(O)R_(b), —C(S)R_(a), —C(O)NR_(a)R_(b), —C(S)NR_(a)R_(b),—NR_(a)C(O)NR_(b)R_(c), NR_(a)C(S)NR_(b)R_(c), —N(R_(a))SOR_(b),—N(R_(a))SO₂R_(b), —NR_(a)C(O)OR_(b), —NR_(a)R_(b), —NR_(a)C(O)R_(b)—,—NR_(a)C(S)R_(b)—, —SONR_(a)R_(b)—, —SO₂NR_(a)R_(b)—, —OR_(a),—OR_(a)C(O)OR_(b)—, —OC(O)NR_(a)R_(b), OC(O)R_(a), —OC(O)NR_(a)R_(b)—,—R_(a)NR_(b)R_(c), —R_(a)OR_(b)—, —SR_(a), —SOR_(a) and —SO₂R_(a),wherein R_(a), R_(b) and R_(c) is independently selected from the groupconsisting of hydrogen, C₁₋₈ alkyl, C₃₋₈ cycloalkyl, C₅₋₆ aryl, C₇₋₁₅arylalkyl, C₂₋₁₀ heterocyclyl, C₁₋₆ heteroaryl, and C₂₋₁₂heteroarylalkyl with heteroatoms selected from N, O, S;wherein C₇₋₁₂ arylalkoxy, C₁₋₈ alkyl, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₂₋₁₀heterocyclyl, C₃₋₈ cycloalkyl, is optionally substituted with one ormore of the groups selected from hydrogen, C₁₋₆ alkyl, C₅₋₆ aryl, C₁₋₆heteroaryl, C₂₋₁₀ heterocyclyl, oxo (═O), C₃₋₈ cycloalkyl, halogen, OH,amino, and cyano;R₃ is selected from the group consisting of hydrogen, substituted orunsubstituted C₁₋₈ alkyl, and C₅₋₆ aryl;R₂ is selected from the group consisting of —OR₇, aniline, amino C₅₋₆aryl, and amino C₁₋₆ heteroaryl,wherein aniline, amino C₅₋₆ aryl, and amino C₁₋₆ heteroaryl, isoptionally substituted with one or more of the groups selected from C₁₋₈alkyl, halogen, OH, amino, and cyano;R₇ is selected from the group consisting of hydrogen, C₁₋₈ alkyl, C₅₋₆aryl, C₂₋₁₀ heterocyclyl and —COR₈, wherein R₈ is selected from thegroup consisting of C₁₋₈ alkyl, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₃₋₈cycloalkyl, and C₂₋₁₀ heterocyclyl.

In an embodiment of the present invention, there is provided a compoundof Formula I

their analogs, tautomeric forms, stereoisomers, polymorphs, solvates,intermediates, pharmaceutically acceptable salts, metabolites, andprodrugs thereof;whereinAr is selected from the group consisting of substituted or unsubstitutedC₅₋₆aryl, C₁₋₆ heteroaryl, and C₂₋₁₀ heterocyclyl with heteroatomsselected from N, O, S;W represents a bond or CR₄R₅, whereinR₄ and R₅ are independently selected from the group consisting ofhydrogen, substituted or unsubstituted C₁₋₈ alkyl, C₅₋₆ aryl, and C₁₋₆heteroaryl with heteroatoms selected from N, O, S;Y is a bond or is selected from the group consisting of substituted orunsubstituted C₁₋₈ alkyl, C₁₋₈ alkenyl, C₁₋₈ alkynyl, C₅₋₆ aryl, C₁₋₆heteroaryl, C₂₋₁₀ heterocyclyl, C₃₋₈ cycloalkyl, —CO—, and —CO—C₂₋₁₀heterocyclyl;wherein C₁₋₈ alkyl, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₂₋₁₀ heterocyclyl, C₃₋₈cycloalkyl, is optionally substituted with one or more of the groupsselected from hydrogen, C₁₋₆ alkyl, oxo (═O), C₃₋₈ cycloalkyl, halogen,OH, and cyano;Z represents a bond or is selected from the group consisting of C₁₋₈alkyl, C₁₋₈ alkenyl, C₁₋₈ alkynyl, C₇₋₁₂-alkylaryl, C₇₋₁₂-alkenylaryl,C₇₋₁₅-arylalkenyl, C₂₋₁₂-alkylheteroaryl, —CO—C₇₋₁₂ alkylaryl, —CO—C₇₋₁₂alkenylaryl, —CONR₆—C₁₋₈ alkyl, —NR₆CO—C₁₋₈ alkyl-, —NR₆—C₁₋₈ alkyl,—O—C₁₋₈ alkyl-, —CONR₆—C₅₋₆ aryl-, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₂₋₁₀heterocyclyl, —CO—C₂₋₁₀ heterocyclyl, —NR₆—CO—OC₁₋₈ alkyl, O—CO—NR₆—C₁₋₈alkyl, —NR₆CO—C₅₋₆ aryl-, —NR₆—C₅₋₆ aryl, —NR₆—C₁₋₆ heteroaryl, —C₁₋₈alkyl-O—C₅₋₆ aryl, —O—C₅₋₆ aryl, O—C₁₋₆ heteroaryl, —NR₆—CO—OC₅₋₆ aryl,—CONR₆—C₇₋₁₂ alkylaryl, —CONR₆—C₇₋₁₂ alkenylaryl, —SO₂—C₇₋₁₂ alkylaryl,—NR₆SO₂—C₇₋₁₂ alkylaryl, C₁₋₈ alkyl-CONR₆—C₅₋₆ aryl, and O—CO—NR₆—C₅₋₆aryl;R₆ is selected from the group consisting of hydrogen, C₁₋₈ alkyl, C₁₋₆haloalkyl, C₃₋₈ cycloalkyl, C₅₋₆ aryl, and C₁₋₆ heteroaryl, withheteroatoms selected from N, O, S;R₁ is selected from the group consisting of hydrogen, halogen hydroxy,nitro, cyano, azido, nitroso, oxo (═O), thioxo (═S), —SO₂—, amino,hydrazino, formyl, C₁₋₈ alkyl, C₁₋₈ haloalkyl, C₁₋₈ alkoxy, C₁₋₈haloalkoxy, C₇₋₁₂ arylalkoxy, C₃₋₈ cycloalkyl, C₃₋₈ cycloalkyloxy, C₅₋₆aryl, C₂₋₁₀ heterocyclyl, C₁₋₆ heteroaryl, alkylamino, —COOR_(a),—C(O)R_(b), —C(S)R_(a), —C(O)NR_(a)R_(b), —C(S)NR_(a)R_(b),—NR_(a)C(O)NR_(b)R_(c), NR_(a)C(S)NR_(b)R_(c), —N(R_(a))SOR_(b),—N(R_(a))SO₂R_(b), —NR_(a)C(O)OR_(b), —NR_(a)R_(b), —NR_(a)C(O)R_(b)—,—NR_(a)C(S)R_(b)—, —SONR_(a)R_(b)—, —SO₂NR_(a)R_(b)—, —OR_(a),—OR_(a)C(O)OR_(b)—, —OC(O)NR_(a)R_(b), OC(O)R_(a), —OC(O)NR_(a)R_(b)—,—R_(a)NR_(b)R_(c), —R_(a)OR_(b)—, —SR_(a), —SOR_(a) and —SO₂R_(a),wherein R_(a), R_(b) and R_(c) is independently selected from the groupconsisting of hydrogen, C₁₋₈ alkyl, C₃₋₈ cycloalkyl, C₅₋₆ aryl, C₇₋₁₅arylalkyl, C₂₋₁₀ heterocyclyl, C₁₋₆ heteroaryl, and C₂₋₁₂heteroarylalkyl with heteroatoms selected from N, O, S;wherein C₇₋₁₂ arylalkoxy, C₁₋₈ alkyl, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₂₋₁₀heterocyclyl, C₃₋₈ cycloalkyl, is optionally substituted with one ormore of the groups selected from hydrogen, C₁₋₆ alkyl, C₅₋₆ aryl, C₁₋₆heteroaryl, C₂₋₁₀ heterocyclyl, oxo (═O), C₃₋₈ cycloalkyl, halogen, OH,amino, and cyano;R₃ is selected from the group consisting of hydrogen, substituted orunsubstituted C₁₋₈ alkyl, and C₅₋₆ aryl;R₂ is selected from the group consisting of —OR₇, aniline, amino C₅₋₆aryl, and amino C₁₋₆ heteroaryl,wherein aniline, amino C₅₋₆ aryl, and amino C₁₋₆ heteroaryl, isoptionally substituted with one or more of the groups selected from C₁₋₈alkyl, halogen, OH, amino, and cyano;R₇ is selected from the group consisting of hydrogen, C₁₋₈ alkyl, C₅₋₆aryl, C₂₋₁₀ heterocyclyl and —COR₈, wherein R₈ is selected from thegroup consisting of C₁₋₈ alkyl, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₃₋₈cycloalkyl, and C₂₋₁₀ heterocyclyl.

In an embodiment of the present invention, there is provided a compoundof Formula I

their analogs, tautomeric forms, stereoisomers, polymorphs, solvates,intermediates, pharmaceutically acceptable salts, metabolites, andprodrugs thereof;whereinAr is selected from the group consisting of substituted or unsubstitutedC₅₋₆aryl, C₁₋₆ heteroaryl, and C₂₋₁₀ heterocyclyl with heteroatomsselected from N, O, S;W represents a bond or CR₄R₅, whereinR₄ and R₅ are independently selected from the group consisting ofhydrogen, substituted or unsubstituted C₁₋₈ alkyl, C₅₋₆ aryl, and C₁₋₆heteroaryl with heteroatoms selected from N, O, S;Y is a bond or is selected from the group consisting of substituted orunsubstituted C₁₋₈ alkyl, C₁₋₈ alkenyl, C₁₋₈ alkynyl, C₅₋₆ aryl, C₁₋₆heteroaryl, C₂₋₁₀ heterocyclyl, C₃₋₈ cycloalkyl, —CO—, and —CO—C₂₋₁₀heterocyclyl;wherein C₁₋₈ alkyl, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₂₋₁₀ heterocyclyl, C₃₋₈cycloalkyl, is optionally substituted with one or more of the groupsselected from hydrogen, C₁₋₆ alkyl, oxo (═O), C₃₋₈ cycloalkyl, halogen,OH, and cyano;Z represents a bond or is selected from the group consisting of C₁₋₈alkyl, C₁₋₈ alkenyl, C₁₋₈ alkynyl, C₇₋₁₂-alkylaryl, C₇₋₁₂-alkenylaryl,C₇₋₁₅-arylalkenyl, C₂₋₁₂-alkylheteroaryl, —CO—C₇₋₁₂ alkylaryl, —CO—C₇₋₁₂alkenylaryl, —CONR₆—C₁₋₈ alkyl, —NR₆CO—C₁₋₈ alkyl-, —NR₆—C₁₋₈ alkyl,—O—C₁₋₈ alkyl-, —CONR₆—C₅₋₆ aryl-, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₂₋₁₀heterocyclyl, —CO—C₂₋₁₀ heterocyclyl, —NR₆—CO—OC₁₋₈ alkyl, O—CO—NR₆—C₁₋₈alkyl, —NR₆CO—C₅₋₆ aryl-, —NR₆—C₅₋₆ aryl, —NR₆—C₁₋₆ heteroaryl, —C₁₋₈alkyl-O—C₅₋₆ aryl, —O—C₅₋₆ aryl, O—C₁₋₆ heteroaryl, —NR₆—CO—OC₅₋₆ aryl,—CONR₆—C₇₋₁₂ alkylaryl, —CONR₆—C₇₋₁₂ alkenylaryl, —SO₂—C₅₋₆ aryl,—SO₂—C₇₋₁₂ alkylaryl, —NR₆SO₂—C₇₋₁₂ alkylaryl, C₁₋₈ alkyl-CONR₆—C₅₋₆aryl, and O—CO—NR₆—C₅₋₆ aryl;R₆ is selected from the group consisting of hydrogen, C₁₋₈ alkyl, C₁₋₆haloalkyl, C₃₋₈ cycloalkyl, C₅₋₆ aryl, and C₁₋₆ heteroaryl, withheteroatoms selected from N, O, S;R₁ is selected from the group consisting of hydrogen, halogen hydroxy,nitro, cyano, azido, nitroso, oxo (═O), thioxo (═S), —SO₂—, amino,hydrazino, formyl, C₁₋₈ alkyl, C₁₋₈ haloalkyl, C₁₋₈ alkoxy, C₁₋₈haloalkoxy, C₇₋₁₂ arylalkoxy, C₃₋₈ cycloalkyl, C₃₋₈ cycloalkyloxy, C₅₋₆aryl, C₂₋₁₀ heterocyclyl, C₁₋₆ heteroaryl, alkylamino, —COOR_(a),—C(O)R_(b), —C(S)R_(a), —C(O)NR_(a)R_(b), —C(S)NR_(a)R_(b),—NR_(a)C(O)NR_(b)R_(c), NR_(a)C(S)NR_(b)R_(c), —N(R_(a))SOR_(b),—N(R_(a))SO₂R_(b), —NR_(a)C(O)OR_(b), —NR_(a)R_(b), —NR_(a)C(O)R_(b)—,—NR_(a)C(S)R_(b)—, —SONR_(a)R_(b)—, —SO₂NR_(a)R_(b)—, —OR_(a),—OR_(a)C(O)OR_(b)—, —OC(O)NR_(a)R_(b), OC(O)R_(a), —OC(O)NR_(a)R_(b)—,—R_(a)NR_(b)R_(c), —R_(a)OR_(b)—, —SR_(a), —SOR_(a) and —SO₂R_(a),wherein R_(a), R_(b) and R_(c) is independently selected from the groupconsisting of hydrogen, C₁₋₈ alkyl, C₃₋₈ cycloalkyl, C₅₋₆ aryl, C₇₋₁₅arylalkyl, C₂₋₁₀ heterocyclyl, C₁₋₆ heteroaryl, and C₂₋₁₂heteroarylalkyl with heteroatoms selected from N, O, S;wherein C₇₋₁₂ arylalkoxy, C₁₋₈ alkyl, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₂₋₁₀heterocyclyl, C₃₋₈ cycloalkyl, is optionally substituted with one ormore of the groups selected from hydrogen, C₁₋₆ alkyl, C₅₋₆ aryl, C₁₋₆heteroaryl, C₂₋₁₀ heterocyclyl, oxo (═O), C₃₋₈ cycloalkyl, halogen, OH,amino, and cyano;R₃ is selected from the group consisting of hydrogen, substituted orunsubstituted C₁₋₈ alkyl, and C₅₋₆ aryl;R₂ is selected from the group consisting of —OR₇, aniline, amino C₅₋₆aryl, and amino C₁₋₆ heteroaryl,wherein aniline, amino C₅₋₆ aryl, and amino C₁₋₆ heteroaryl, isoptionally substituted with one or more of the groups selected from C₁₋₈alkyl, halogen, OH, amino, and cyano;R₇ is selected from the group consisting of hydrogen, C₁₋₈ alkyl, C₅₋₆aryl, C₂₋₁₀ heterocyclyl and —COR₈, wherein R₈ is selected from thegroup consisting of C₁₋₈ alkyl, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₃₋₈cycloalkyl, and C₂₋₁₀ heterocyclyl.

In an embodiment of the present invention, there is provided a compoundof Formula I

their analogs, tautomeric forms, stereoisomers, polymorphs, solvates,intermediates, pharmaceutically acceptable salts, metabolites, andprodrugs thereof;whereinAr is selected from the group consisting of substituted or unsubstitutedC₅₋₆aryl, C₁₋₆ heteroaryl, and C₂₋₁₀ heterocyclyl with heteroatomsselected from N, O, S;W represents a bond or CR₄R₅, whereinR₄ and R₅ are independently selected from the group consisting ofhydrogen, substituted or unsubstituted C₁₋₈ alkyl, C₅₋₆ aryl, and C₁₋₆heteroaryl with heteroatoms selected from N, O, S;Y is a bond or is selected from the group consisting of substituted orunsubstituted C₁₋₈ alkyl, C₁₋₈ alkenyl, C₁₋₈ alkynyl, C₅₋₆ aryl, C₁₋₆heteroaryl, C₂₋₁₀ heterocyclyl, C₃₋₈ cycloalkyl, —CO—, and —CO—C₂₋₁₀heterocyclyl;wherein C₁₋₈ alkyl, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₂₋₁₀ heterocyclyl, C₃₋₈cycloalkyl, is optionally substituted with one or more of the groupsselected from hydrogen, C₁₋₆ alkyl, oxo (═O), C₃₋₈ cycloalkyl, halogen,OH, and cyano;Z represents a bond or is selected from the group consisting of C₁₋₈alkyl, C₁₋₈ alkenyl, C₁₋₈ alkynyl, C₇₋₁₂-alkylaryl, C₇₋₁₂-alkenylaryl,C₇₋₁₅-arylalkenyl, C₂₋₁₂-alkylheteroaryl, —CO—C₇₋₁₂ alkylaryl, —CO—C₇₋₁₂alkenylaryl, —CONR₆—C₁₋₈ alkyl, —NR₆CO—C₁₋₈ alkyl-, —NR₆—C₁₋₈ alkyl,—O—C₁₋₈ alkyl-, —CONR₆—C₅₋₆ aryl-, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₂₋₁₀heterocyclyl, —CO—C₂₋₁₀ heterocyclyl, —NR₆—CO—OC₁₋₈ alkyl, O—CO—NR₆—C₁₋₈alkyl, —NR₆CO—C₅₋₆ aryl-, —NR₆—C₅₋₆ aryl, —NR₆—C₁₋₆ heteroaryl, —C₁₋₈alkyl-O—C₅₋₆ aryl, —O—C₅₋₆ aryl, O—C₁₋₆ heteroaryl, —NR₆—CO—OC₅₋₆ aryl,—CONR₆—C₇₋₁₂ alkylaryl, —CONR₆—C₇₋₁₂ alkenylaryl, —SO₂—C₅₋₆ aryl,—NR₆SO₂—C₇₋₁₂ alkylaryl, C₁₋₈ alkyl-CONR₆—C₅₋₆ aryl, and O—CO—NR₆—C₅₋₆aryl;R₆ is selected from the group consisting of hydrogen, C₁₋₈ alkyl, C₁₋₆haloalkyl, C₃₋₈ cycloalkyl, C₅₋₆ aryl, and C₁₋₆ heteroaryl, withheteroatoms selected from N, O, S;R₁ is selected from the group consisting of hydrogen, halogen hydroxy,nitro, cyano, azido, nitroso, oxo (═O), thioxo (═S), —SO₂—, amino,hydrazino, formyl, C₁₋₈ alkyl, C₁₋₈ haloalkyl, C₁₋₈ alkoxy, C₁₋₈haloalkoxy, C₇₋₁₂ arylalkoxy, C₃₋₈ cycloalkyl, C₃₋₈ cycloalkyloxy, C₅₋₆aryl, C₂₋₁₀ heterocyclyl, C₁₋₆ heteroaryl, alkylamino, —COOR_(a),—C(O)R_(b), —C(S)R_(a), —C(O)NR_(a)R_(b), —C(S)NR_(a)R_(b),—NR_(a)C(O)NR_(b)R_(c), NR_(a)C(S)NR_(b)R_(c), —N(R_(a))SOR_(b),—N(R_(a))SO₂R_(b), —NR_(a)C(O)OR_(b), —NR_(a)R_(b), —NR_(a)C(O)R_(b)—,—NR_(a)C(S)R_(b)—, —SONR_(a)R_(b)—, —SO₂NR_(a)R_(b)—, —OR_(a),—OR_(a)C(O)OR_(b)—, —OC(O)NR_(a)R_(b), OC(O)R_(a), —OC(O)NR_(a)R_(b)—,—R_(a)NR_(b)R_(c), —R_(a)OR_(b)—, —SR_(a), —SOR_(a) and —SO₂R_(a),wherein R_(a), R_(b) and R_(c) is independently selected from the groupconsisting of hydrogen, C₁₋₈ alkyl, C₃₋₈ cycloalkyl, C₅₋₆ aryl, C₇₋₁₅arylalkyl, C₂₋₁₀ heterocyclyl, C₁₋₆ heteroaryl, and C₂₋₁₂heteroarylalkyl with heteroatoms selected from N, O, S;wherein C₇₋₁₂ arylalkoxy, C₁₋₈ alkyl, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₂₋₁₀heterocyclyl, C₃₋₈ cycloalkyl, is optionally substituted with one ormore of the groups selected from hydrogen, C₁₋₆ alkyl, C₅₋₆ aryl, C₁₋₆heteroaryl, C₂₋₁₀ heterocyclyl, oxo (═O), C₃₋₈ cycloalkyl, halogen, OH,amino, and cyano;R₃ is selected from the group consisting of hydrogen, substituted orunsubstituted C₁₋₈ alkyl, and C₅₋₆ aryl;R₂ is selected from the group consisting of —OR₇, aniline, amino C₅₋₆aryl, and amino C₁₋₆ heteroaryl,wherein aniline, amino C₅₋₆ aryl, and amino C₁₋₆ heteroaryl, isoptionally substituted with one or more of the groups selected from C₁₋₈alkyl, halogen, OH, amino, and cyano;R₇ is selected from the group consisting of hydrogen, C₁₋₈ alkyl, C₅₋₆aryl, C₂₋₁₀ heterocyclyl and —COR₈, wherein R₈ is selected from thegroup consisting of C₁₋₈ alkyl, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₃₋₈cycloalkyl, and C₂₋₁₀ heterocyclyl.

In an embodiment of the present invention, there is provided a compoundof Formula I

their analogs, tautomeric forms, stereoisomers, polymorphs, solvates,intermediates, pharmaceutically acceptable salts, metabolites, andprodrugs thereof;whereinAr is selected from the group consisting of substituted or unsubstitutedC₅₋₆ aryl, C₁₋₆ heteroaryl, and C₂₋₁₀ heterocyclyl with heteroatomsselected from N, O, S;W represents a bond or CR₄R₅, whereinR₄ and R₅ are independently selected from the group consisting ofhydrogen, substituted or unsubstituted C₁₋₈ alkyl, C₅₋₆ aryl, and C₁₋₆heteroaryl with heteroatoms selected from N, O, S;Y is a bond or is selected from the group consisting of substituted orunsubstituted C₁₋₈ alkyl, C₁₋₈ alkenyl, C₁₋₈ alkynyl, C₅₋₆ aryl, C₁₋₆heteroaryl, C₂₋₁₀ heterocyclyl, C₃₋₈ cycloalkyl, —CO—, and —CO—C₂₋₁₀heterocyclyl;wherein C₁₋₈ alkyl, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₂₋₁₀ heterocyclyl, C₃₋₈cycloalkyl, is optionally substituted with one or more of the groupsselected from hydrogen, C₁₋₆ alkyl, oxo (═O), C₃₋₈ cycloalkyl, halogen,OH, and cyano;Z represents a bond or is selected from the group consisting of C₁₋₈alkyl, C₁₋₈ alkenyl, C₁₋₈ alkynyl, C₇₋₁₂-alkylaryl, C₇₋₁₂-alkenylaryl,C₇₋₁₅-arylalkenyl, C₂₋₁₂-alkylheteroaryl, —CO—C₇₋₁₂ alkylaryl, —CO—C₇₋₁₂alkenylaryl, —CONR₆—C₁₋₈ alkyl, —NR₆CO—C₁₋₈ alkyl-, —NR₆—C₁₋₈ alkyl,—O—C₁₋₈ alkyl-, —CONR₆—C₅₋₆ aryl-, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₂₋₁₀heterocyclyl, —CO—C₂₋₁₀ heterocyclyl, —NR₆—CO—OC₁₋₈ alkyl, O—CO—NR₆—C₁₋₈alkyl, —NR₆CO—C₅₋₆ aryl-, —NR₆—C₅₋₆ aryl, —NR₆—C₁₋₆ heteroaryl, —C₁₋₈alkyl-O—C₅₋₆ aryl, —O—C₅₋₆ aryl, O—C₁₋₆ heteroaryl, —NR₆—CO—OC₅₋₆ aryl,—CONR₆—C₇₋₁₂ alkylaryl, —CONR₆—C₇₋₁₂ alkenylaryl, —SO₂—C₅₋₆ aryl,—SO₂—C₇₋₁₂ alkylaryl, —NR₆SO₂—C₇₋₁₂ alkylaryl, C₁₋₈ alkyl-CONR₆—C₅₋₆aryl, and O—CO—NR₆—C₅₋₆ aryl;R₆ is selected from the group consisting of hydrogen, C₁₋₈ alkyl, C₁₋₆haloalkyl, C₃₋₈ cycloalkyl, C₅₋₆ aryl, and C₁₋₆ heteroaryl, withheteroatoms selected from N, O, S;R₁ is selected from the group consisting of hydrogen, halogen hydroxy,nitro, cyano, azido, nitroso, oxo (═O), thioxo (═S), —SO₂—, amino,hydrazino, formyl, C₁₋₈ alkyl, C₁₋₈ haloalkyl, C₁₋₈ alkoxy, C₁₋₈haloalkoxy, C₇₋₁₂ arylalkoxy, C₃₋₈ cycloalkyl, C₃₋₈ cycloalkyloxy, C₅₋₆aryl, C₂₋₁₀ heterocyclyl, C₁₋₆ heteroaryl, alkylamino, —COOR_(a),—C(O)R_(b), —C(S)R_(a), —C(O)NR_(a)R_(b), —C(S)NR_(a)R_(b),—NR_(a)C(O)NR_(b)R_(c), NR_(a)C(S)NR_(b)R_(c), —N(R_(a))SOR_(b),—N(R_(a))SO₂R_(b), —NR_(a)C(O)OR_(b), —NR_(a)R_(b), —NR_(a)C(O)R_(b)—,—NR_(a)C(S)R_(b)—, —SONR_(a)R_(b)—, —SO₂NR_(a)R_(b)—, —OR_(a),—OR_(a)C(O)OR_(b)—, —OC(O)NR_(a)R_(b), OC(O)R_(a), —OC(O)NR_(a)R_(b)—,—R_(a)NR_(b)R_(c), —R_(a)OR_(b)—, —SR_(a), —SOR_(a) and —SO₂R_(a),wherein R_(a), R_(b) and R_(c) is independently selected from the groupconsisting of hydrogen, C₁₋₈ alkyl, C₃₋₈ cycloalkyl, C₅₋₆ aryl, C₇₋₁₅arylalkyl, C₂₋₁₀ heterocyclyl, C₁₋₆ heteroaryl, and C₂₋₁₂heteroarylalkyl with heteroatoms selected from N, O, S;wherein C₇₋₁₂ arylalkoxy, C₁₋₈ alkyl, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₂₋₁₀heterocyclyl, C₃₋₈ cycloalkyl, is optionally substituted with one ormore of the groups selected from hydrogen, C₁₋₆ alkyl, C₅₋₆ aryl, C₁₋₆heteroaryl, C₂₋₁₀ heterocyclyl, oxo (═O), C₃₋₈ cycloalkyl, halogen, OH,amino, and cyano;R₃ is selected from the group consisting of hydrogen, substituted orunsubstituted C₁₋₈ alkyl, and C₅₋₆ aryl;R₂ is selected from the group consisting of —OR₇, aniline, amino C₅₋₆aryl, and amino C₁₋₆ heteroaryl,wherein aniline, amino C₅₋₆ aryl, and amino C₁₋₆ heteroaryl, isoptionally substituted with one or more of the groups selected from C₁₋₈alkyl, halogen, OH, amino, and cyano;R₇ is selected from the group consisting of hydrogen, C₁₋₈ alkyl, C₅₋₆aryl, C₂₋₁₀ heterocyclyl and —COR₈, wherein R₈ is selected from thegroup consisting of C₁₋₈ alkyl, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₃₋₈cycloalkyl, and C₂₋₁₀ heterocyclyl.

In an embodiment of the present invention, there is provided a compoundof Formula I

their analogs, tautomeric forms, stereoisomers, polymorphs, solvates,intermediates, pharmaceutically acceptable salts, metabolites, andprodrugs thereof;whereinAr is selected from the group consisting of substituted or unsubstitutedC₅₋₆aryl, C₁₋₆ heteroaryl, and C₂₋₁₀ heterocyclyl with heteroatomsselected from N, O, S;W represents a bond or CR₄R₅, whereinR₄ and R₅ are independently selected from the group consisting ofhydrogen, substituted or unsubstituted C₁₋₈ alkyl, C₅₋₆ aryl, and C₁₋₆heteroaryl with heteroatoms selected from N, O, S;Y is a bond or is selected from the group consisting of substituted orunsubstituted C₁₋₈ alkyl, C₁₋₈ alkenyl, C₁₋₈ alkynyl, C₅₋₆ aryl, C₁₋₆heteroaryl, C₂₋₁₀ heterocyclyl, C₃₋₈ cycloalkyl, —CO—, and —CO—C₂₋₁₀heterocyclyl;wherein C₁₋₈ alkyl, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₂₋₁₀ heterocyclyl, C₃₋₈cycloalkyl, is optionally substituted with one or more of the groupsselected from hydrogen, C₁₋₆ alkyl, oxo (═O), C₃₋₈ cycloalkyl, halogen,OH, and cyano;Z represents a bond or is selected from the group consisting of C₁₋₈alkyl, C₁₋₈ alkenyl, C₁₋₈ alkynyl, C₇₋₁₂-alkylaryl, C₇₋₁₂-alkenylaryl,C₇₋₁₅-arylalkenyl, C₂₋₁₂-alkylheteroaryl, —CO—C₇₋₁₂ alkylaryl,—CONR₆—C₁₋₈ alkyl, —NR₆CO—C₁₋₈ alkyl-, —NR₆—C₁₋₈ alkyl, —O—C₁₋₈ alkyl-,—CONR₆—C₅₋₆ aryl-, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₂₋₁₀ heterocyclyl,—CO—C₂₋₁₀ heterocyclyl, —NR₆—CO—OC₁₋₈ alkyl, O—CO—NR₆—C₁₋₈ alkyl,—NR₆CO—C₅₋₆ aryl-, —NR₆—C₅₋₆ aryl, —NR₆—C₁₋₆ heteroaryl, —C₁₋₈alkyl-O—C₅₋₆ aryl, —O—C₅₋₆ aryl, O—C₁₋₆ heteroaryl, —NR₆—CO—OC₅₋₆ aryl,—CONR₆—C₇₋₁₂ alkylaryl, —CONR₆—C₇₋₁₂ alkenylaryl, —SO₂—C₅₋₆ aryl,—SO₂—C₇₋₁₂ alkylaryl, —NR₆SO₂—C₇₋₁₂ alkylaryl, C₁₋₈ alkyl-CONR₆—C₅₋₆aryl, and O—CO—NR₆—C₅₋₆ aryl;R₆ is selected from the group consisting of hydrogen, C₁₋₈ alkyl, C₁₋₆haloalkyl, C₃₋₈ cycloalkyl, C₅₋₆ aryl, and C₁₋₆ heteroaryl, withheteroatoms selected from N, O, S;R₁ is selected from the group consisting of hydrogen, halogen hydroxy,nitro, cyano, azido, nitroso, oxo (═O), thioxo (═S), —SO₂—, amino,hydrazino, formyl, C₁₋₈ alkyl, C₁₋₈ haloalkyl, C₁₋₈ alkoxy, C₁₋₈haloalkoxy, C₇₋₁₂ arylalkoxy, C₃₋₈ cycloalkyl, C₃₋₈ cycloalkyloxy, C₅₋₆aryl, C₂₋₁₀ heterocyclyl, C₁₋₆ heteroaryl, alkylamino, —COOR_(a),—C(O)R_(b), —C(S)R_(a), —C(O)NR_(a)R_(b), —C(S)NR_(a)R_(b),—NR_(a)C(O)NR_(b)R_(c), NR_(a)C(S)NR_(b)R_(c), —N(R_(a))SOR_(b),—N(R_(a))SO₂R_(b), —NR_(a)C(O)OR_(b), —NR_(a)R_(b), —NR_(a)C(O)R_(b)—,—NR_(a)C(S)R_(b)—, —SONR_(a)R_(b)—, —SO₂NR_(a)R_(b)—, —OR_(a),—OR_(a)C(O)OR_(b)—, —OC(O)NR_(a)R_(b), OC(O)R_(a), —OC(O)NR_(a)R_(b)—,—R_(a)NR_(b)R_(c), —R_(a)OR_(b)—, —SR_(a), —SOR_(a) and —SO₂R_(a),wherein R_(a), R_(b) and R_(c) is independently selected from the groupconsisting of hydrogen, C₁₋₈ alkyl, C₃₋₈ cycloalkyl, C₅₋₆ aryl, C₇₋₁₅arylalkyl, C₂₋₁₀ heterocyclyl, C₁₋₆ heteroaryl, and C₂₋₁₂heteroarylalkyl with heteroatoms selected from N, O, S;wherein C₇₋₁₂ arylalkoxy, C₁₋₈ alkyl, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₂₋₁₀heterocyclyl, C₃₋₈ cycloalkyl, is optionally substituted with one ormore of the groups selected from hydrogen, C₁₋₆ alkyl, C₅₋₆ aryl, C₁₋₆heteroaryl, C₂₋₁₀ heterocyclyl, oxo (═O), C₃₋₈ cycloalkyl, halogen, OH,amino, and cyano;R₃ is selected from the group consisting of hydrogen, substituted orunsubstituted C₁₋₈ alkyl, and C₅₋₆ aryl;R₂ is selected from the group consisting of —OR₇, aniline, amino C₅₋₆aryl, and amino C₁₋₆ heteroaryl,wherein aniline, amino C₅₋₆ aryl, and amino C₁₋₆ heteroaryl, isoptionally substituted with one or more of the groups selected from C₁₋₈alkyl, halogen, OH, amino, and cyano;R₇ is selected from the group consisting of hydrogen, C₁₋₈ alkyl, C₅₋₆aryl, C₂₋₁₀ heterocyclyl and —COR₈, wherein R₈ is selected from thegroup consisting of C₁₋₈ alkyl, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₃₋₈cycloalkyl, and C₂₋₁₀ heterocyclyl.

In an embodiment of the present invention, there is provided a compoundof Formula I

their analogs, tautomeric forms, stereoisomers, polymorphs, solvates,intermediates, pharmaceutically acceptable salts, metabolites, andprodrugs thereof;whereinAr is selected from the group consisting of substituted or unsubstitutedC₅₋₆aryl, C₁₋₆ heteroaryl, and C₂₋₁₀ heterocyclyl with heteroatomsselected from N, O, S;W represents a bond or CR₄R₅, whereinR₄ and R₅ are independently selected from the group consisting ofhydrogen, substituted or unsubstituted C₁₋₈ alkyl, C₅₋₆ aryl, and C₁₋₆heteroaryl with heteroatoms selected from N, O, S;Y is a bond or is selected from the group consisting of substituted orunsubstituted C₁₋₈ alkyl, C₁₋₈ alkenyl, C₁₋₈ alkynyl, C₅₋₆ aryl, C₁₋₆heteroaryl, C₂₋₁₀ heterocyclyl, C₃₋₈ cycloalkyl, —CO—, and —CO—C₂₋₁₀heterocyclyl;wherein C₁₋₈ alkyl, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₂₋₁₀ heterocyclyl, C₃₋₈cycloalkyl, is optionally substituted with one or more of the groupsselected from hydrogen, C₁₋₆ alkyl, oxo (═O), C₃₋₈ cycloalkyl, halogen,OH, and cyano;Z represents a bond or is selected from the group consisting of C₁₋₈alkyl, C₁₋₈ alkenyl, C₁₋₈ alkynyl, C₇₋₁₂-alkylaryl, C₇₋₁₂-alkenylaryl,C₇₋₁₅-arylalkenyl, C₂₋₁₂-alkylheteroaryl, —CO—C₇₋₁₂ alkylaryl, —CO—C₇₋₁₂alkenylaryl, —CONR₆—C₁₋₈ alkyl, —NR₆CO—C₁₋₈ alkyl-, —NR₆—C₁₋₈ alkyl,—O—C₁₋₈ alkyl-, —CONR₆—C₅₋₆ aryl-, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₂₋₁₀heterocyclyl, —CO—C₂₋₁₀ heterocyclyl, —NR₆—CO—OC₁₋₈ alkyl, O—CO—NR₆—C₁₋₈alkyl, —NR₆CO—C₅₋₆ aryl-, —NR₆—C₅₋₆ aryl, —NR₆—C₁₋₆ heteroaryl, —C₁₋₈alkyl-O—C₅₋₆ aryl, O—C₁₋₆ heteroaryl, —NR₆—CO—OC₅₋₆ aryl, —CONR₆—C₇₋₁₂alkylaryl, —CONR₆—C₇₋₁₂ alkenylaryl, —SO₂—C₅₋₆ aryl, —SO₂—C₇₋₁₂alkylaryl, —NR₆SO₂—C₇₋₁₂ alkylaryl, C₁₋₈ alkyl-CONR₆—C₅₋₆ aryl, andO—CO—NR₆—C₅₋₆ aryl;R₆ is selected from the group consisting of hydrogen, C₁₋₈ alkyl, C₁₋₆haloalkyl, C₃₋₈ cycloalkyl, C₅₋₆ aryl, and C₁₋₆ heteroaryl, withheteroatoms selected from N, O, S;R₁ is selected from the group consisting of hydrogen, halogen hydroxy,nitro, cyano, azido, nitroso, oxo (═O), thioxo (═S), —SO₂—, amino,hydrazino, formyl, C₁₋₈ alkyl, C₁₋₈ haloalkyl, C₁₋₈ alkoxy, C₁₋₈haloalkoxy, C₇₋₁₂ arylalkoxy, C₃₋₈ cycloalkyl, C₃₋₈ cycloalkyloxy, C₅₋₆aryl, C₂₋₁₀ heterocyclyl, C₁₋₆ heteroaryl, alkylamino, —COOR_(a),—C(O)R_(b), —C(S)R_(a), —C(O)NR_(a)R_(b), —C(S)NR_(a)R_(b),—NR_(a)C(O)NR_(b)R_(c), NR_(a)C(S)NR_(b)R_(c), —N(R_(a))SOR_(b),—N(R_(a))SO₂R_(b), —NR_(a)C(O)OR_(b), —NR_(a)R_(b), —NR_(a)C(O)R_(b)—,—NR_(a)C(S)R_(b)—, —SONR_(a)R_(b)—, —SO₂NR_(a)R_(b)—, —OR_(a),—OR_(a)C(O)OR_(b)—, —OC(O)NR_(a)R_(b), OC(O)R_(a), —OC(O)NR_(a)R_(b)—,—R_(a)NR_(b)R_(c), —R_(a)OR_(b)—, —SR_(a), —SOR_(a) and —SO₂R_(a),wherein R_(a), R_(b) and R_(c) is independently selected from the groupconsisting of hydrogen, C₁₋₈ alkyl, C₃₋₈ cycloalkyl, C₅₋₆ aryl, C₇₋₁₅arylalkyl, C₂₋₁₀ heterocyclyl, C₁₋₆ heteroaryl, and C₂₋₁₂heteroarylalkyl with heteroatoms selected from N, O, S;wherein C₇₋₁₂ arylalkoxy, C₁₋₈ alkyl, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₂₋₁₀heterocyclyl, C₃₋₈ cycloalkyl, is optionally substituted with one ormore of the groups selected from hydrogen, C₁₋₆ alkyl, C₅₋₆ aryl, C₁₋₆heteroaryl, C₂₋₁₀ heterocyclyl, oxo (═O), C₃₋₈ cycloalkyl, halogen, OH,amino, and cyano;R₃ is selected from the group consisting of hydrogen, substituted orunsubstituted C₁₋₈ alkyl, and C₅₋₆ aryl;R₂ is selected from the group consisting of —OR₇, aniline, amino C₅₋₆aryl, and amino C₁₋₆ heteroaryl,wherein aniline, amino C₅₋₆ aryl, and amino C₁₋₆ heteroaryl, isoptionally substituted with one or more of the groups selected from C₁₋₈alkyl, halogen, OH, amino, and cyano;R₇ is selected from the group consisting of hydrogen, C₁₋₈ alkyl, C₅₋₆aryl, C₂₋₁₀ heterocyclyl and —COR₈, wherein R₈ is selected from thegroup consisting of C₁₋₈ alkyl, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₃₋₈cycloalkyl, and C₂₋₁₀ heterocyclyl.

In an embodiment of the present invention, there is provided a compoundof Formula I

their analogs, tautomeric forms, stereoisomers, polymorphs, solvates,intermediates, pharmaceutically acceptable salts, metabolites, andprodrugs thereof;whereinAr is selected from the group consisting of substituted or unsubstitutedC₅₋₆aryl, C₁₋₆ heteroaryl, and C₂₋₁₀ heterocyclyl with heteroatomsselected from N, O, S;W represents a bond or CR₄R₅, whereinR₄ and R₅ are independently selected from the group consisting ofhydrogen, substituted or unsubstituted C₁₋₈ alkyl, C₅₋₆ aryl, and C₁₋₆heteroaryl with heteroatoms selected from N, O, S;Y is a bond or is selected from the group consisting of substituted orunsubstituted C₁₋₈ alkyl, C₁₋₈ alkenyl, C₁₋₈ alkynyl, C₅₋₆ aryl, C₁₋₆heteroaryl, C₂₋₁₀ heterocyclyl, C₃₋₈ cycloalkyl, —CO—, and —CO—C₂₋₁₀heterocyclyl;wherein C₁₋₈ alkyl, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₂₋₁₀ heterocyclyl, C₃₋₈cycloalkyl, is optionally substituted with one or more of the groupsselected from hydrogen, C₁₋₆ alkyl, oxo (═O), C₃₋₈ cycloalkyl, halogen,OH, and cyano;Z represents a bond or is selected from the group consisting of C₁₋₈alkyl, C₁₋₈ alkenyl, C₁₋₈ alkynyl, C₇₋₁₂-alkylaryl, C₇₋₁₂-alkenylaryl,C₇₋₁₅-arylalkenyl, C₂₋₁₂-alkylheteroaryl, —CO—C₇₋₁₂ alkylaryl, —CO—C₇₋₁₂alkenylaryl, —CONR₆—C₁₋₈ alkyl, —NR₆CO—C₁₋₈ alkyl-, —NR₆—C₁₋₈ alkyl,—O—C₁₋₈ alkyl-, —CONR₆—C₅₋₆ aryl-, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₂₋₁₀heterocyclyl, —CO—C₂₋₁₀ heterocyclyl, —NR₆—CO—OC₁₋₈ alkyl, O—CO—NR₆—C₁₋₈alkyl, —NR₆CO—C₅₋₆ aryl-, —NR₆—C₅₋₆ aryl, —NR₆—C₁₋₆ heteroaryl, —C₁₋₈alkyl-O—C₅₋₆ aryl, —O—C₅₋₆ aryl, —NR₆—CO—OC₅₋₆ aryl, —CONR₆—C₇₋₁₂alkylaryl, —CONR₆—C₇₋₁₂ alkenylaryl, —SO₂—C₅₋₆ aryl, —SO₂—C₇₋₁₂alkylaryl, —NR₆SO₂—C₇₋₁₂ alkylaryl, C₁₋₈ alkyl-CONR₆—C₅₋₆ aryl, andO—CO—NR₆—C₅₋₆ aryl;R₆ is selected from the group consisting of hydrogen, C₁₋₈ alkyl, C₁₋₆haloalkyl, C₃₋₈ cycloalkyl, C₅₋₆ aryl, and C₁₋₆ heteroaryl, withheteroatoms selected from N, O, S;R₁ is selected from the group consisting of hydrogen, halogen hydroxy,nitro, cyano, azido, nitroso, oxo (═O), thioxo (═S), —SO₂—, amino,hydrazino, formyl, C₁₋₈ alkyl, C₁₋₈ haloalkyl, C₁₋₈ alkoxy, C₁₋₈haloalkoxy, C₇₋₁₂ arylalkoxy, C₃₋₈ cycloalkyl, C₃₋₈ cycloalkyloxy, C₅₋₆aryl, C₂₋₁₀ heterocyclyl, C₁₋₆ heteroaryl, alkylamino, —COOR_(a),—C(O)R_(b), —C(S)R_(a), —C(O)NR_(a)R_(b), —C(S)NR_(a)R_(b),—NR_(a)C(O)NR_(b)R_(c), NR_(a)C(S)NR_(b)R_(c), —N(R_(a))SOR_(b),—N(R_(a))SO₂R_(b), —NR_(a)C(O)OR_(b), —NR_(a)R_(b), —NR_(a)C(O)R_(b)—,—NR_(a)C(S)R_(b)—, —SONR_(a)R_(b)—, —SO₂NR_(a)R_(b)—, —OR_(a),—OR_(a)C(O)OR_(b)—, —OC(O)NR_(a)R_(b), OC(O)R_(a), —OC(O)NR_(a)R_(b)—,—R_(a)NR_(b)R_(c), —R_(a)OR_(b)—, —SR_(a), —SOR_(a) and —SO₂R_(a),wherein R_(a), R_(b) and R_(c) is independently selected from the groupconsisting of hydrogen, C₁₋₈ alkyl, C₃₋₈ cycloalkyl, C₅₋₆ aryl, C₇₋₁₅arylalkyl, C₂₋₁₀ heterocyclyl, C₁₋₆ heteroaryl, and C₂₋₁₂heteroarylalkyl with heteroatoms selected from N, O, S;wherein C₇₋₁₂ arylalkoxy, C₁₋₈ alkyl, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₂₋₁₀heterocyclyl, C₃₋₈ cycloalkyl, is optionally substituted with one ormore of the groups selected from hydrogen, C₁₋₆ alkyl, C₅₋₆ aryl, C₁₋₆heteroaryl, C₂₋₁₀ heterocyclyl, oxo (═O), C₃₋₈ cycloalkyl, halogen, OH,amino, and cyano;R₃ is selected from the group consisting of hydrogen, substituted orunsubstituted C₁₋₈ alkyl, and C₅₋₆ aryl;R₂ is selected from the group consisting of —OR₇, aniline, amino C₅₋₆aryl, and amino C₁₋₆ heteroaryl,wherein aniline, amino C₅₋₆ aryl, and amino C₁₋₆ heteroaryl, isoptionally substituted with one or more of the groups selected from C₁₋₈alkyl, halogen, OH, amino, and cyano;R₇ is selected from the group consisting of hydrogen, C₁₋₈ alkyl, C₅₋₆aryl, C₂₋₁₀ heterocyclyl and —COR₈, wherein R₈ is selected from thegroup consisting of C₁₋₈ alkyl, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₃₋₈cycloalkyl, and C₂₋₁₀ heterocyclyl.

In an embodiment of the present invention, there is provided a compoundof Formula I

their analogs, tautomeric forms, stereoisomers, polymorphs, solvates,intermediates, pharmaceutically acceptable salts, metabolites, andprodrugs thereof;whereinAr is selected from the group consisting of substituted or unsubstitutedC₅₋₆aryl, C₁₋₆ heteroaryl, and C₂₋₁₀ heterocyclyl with heteroatomsselected from N, O, S;W represents a bond or CR₄R₅, whereinR₄ and R₅ are independently selected from the group consisting ofhydrogen, substituted or unsubstituted C₁₋₈ alkyl, C₅₋₆ aryl, and C₁₋₆heteroaryl with heteroatoms selected from N, O, S;Y is a bond or is selected from the group consisting of substituted orunsubstituted C₁₋₈ alkyl, C₁₋₈ alkenyl, C₁₋₈ alkynyl, C₅₋₆ aryl, C₁₋₆heteroaryl, C₂₋₁₀ heterocyclyl, C₃₋₈ cycloalkyl, —CO—, and —CO—C₂₋₁₀heterocyclyl;wherein C₁₋₈ alkyl, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₂₋₁₀ heterocyclyl, C₃₋₈cycloalkyl, is optionally substituted with one or more of the groupsselected from hydrogen, C₁₋₆ alkyl, oxo (═O), C₃₋₈ cycloalkyl, halogen,OH, and cyano;Z represents a bond or is selected from the group consisting of C₁₋₈alkyl, C₁₋₈ alkenyl, C₁₋₈ alkynyl, C₇₋₁₂-alkylaryl, C₇₋₁₂-alkenylaryl,C₇₋₁₅-arylalkenyl, C₂₋₁₂-alkylheteroaryl, —CO—C₇₋₁₂ alkylaryl, —CO—C₇₋₁₂alkenylaryl, —CONR₆—C₁₋₈ alkyl, —NR₆CO—C₁₋₈ alkyl-, —NR₆—C₁₋₈ alkyl,—O—C₁₋₈ alkyl-, —CONR₆—C₅₋₆ aryl-, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₂₋₁₀heterocyclyl, —CO—C₂₋₁₀ heterocyclyl, —NR₆—CO—OC₁₋₈ alkyl, O—CO—NR₆—C₁₋₈alkyl, —NR₆CO—C₅₋₆ aryl-, —NR₆—C₅₋₆ aryl, —C₁₋₈ alkyl-O—C₅₋₆ aryl,—O—C₅₋₆ aryl, O—C₁₋₆ heteroaryl, —NR₆—CO—OC₅₋₆ aryl, —CONR₆—C₇₋₁₂alkylaryl, —CONR₆—C₇₋₁₂ alkenylaryl, —SO₂—C₅₋₆ aryl, —SO₂—C₇₋₁₂alkylaryl, —NR₆SO₂—C₇₋₁₂ alkylaryl, C₁₋₈ alkyl-CONR₆—C₅₋₆ aryl, andO—CO—NR₆—C₅₋₆ aryl;R₆ is selected from the group consisting of hydrogen, C₁₋₈ alkyl, C₁₋₆haloalkyl, C₃₋₈ cycloalkyl, C₅₋₆ aryl, and C₁₋₆ heteroaryl, withheteroatoms selected from N, O, S;R₁ is selected from the group consisting of hydrogen, halogen hydroxy,nitro, cyano, azido, nitroso, oxo (═O), thioxo (═S), —SO₂—, amino,hydrazino, formyl, C₁₋₈ alkyl, C₁₋₈ haloalkyl, C₁₋₈ alkoxy, C₁₋₈haloalkoxy, C₇₋₁₂ arylalkoxy, C₃₋₈ cycloalkyl, C₃₋₈ cycloalkyloxy, C₅₋₆aryl, C₂₋₁₀ heterocyclyl, C₁₋₆ heteroaryl, alkylamino, —COOR_(a),—C(O)R_(b), —C(S)R_(a), —C(O)NR_(a)R_(b), —C(S)NR_(a)R_(b),—NR_(a)C(O)NR_(b)R_(c), NR_(a)C(S)NR_(b)R_(c), —N(R_(a))SOR_(b),—N(R_(a))SO₂R_(b), —NR_(a)C(O)OR_(b), —NR_(a)R_(b), —NR_(a)C(O)R_(b)—,—NR_(a)C(S)R_(b)—, —SONR_(a)R_(b)—, —SO₂NR_(a)R_(b)—, —OR_(a),—OR_(a)C(O)OR_(b)—, —OC(O)NR_(a)R_(b), OC(O)R_(a), —OC(O)NR_(a)R_(b)—,—R_(a)NR_(b)R_(c), —R_(a)OR_(b)—, —SR_(a), —SOR_(a) and —SO₂R_(a),wherein R_(a), R_(b) and R_(c) is independently selected from the groupconsisting of hydrogen, C₁₋₈ alkyl, C₃₋₈ cycloalkyl, C₅₋₆ aryl, C₇₋₁₅arylalkyl, C₂₋₁₀ heterocyclyl, C₁₋₆ heteroaryl, and C₂₋₁₂heteroarylalkyl with heteroatoms selected from N, O, S;wherein C₇₋₁₂ arylalkoxy, C₁₋₈ alkyl, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₂₋₁₀heterocyclyl, C₃₋₈ cycloalkyl, is optionally substituted with one ormore of the groups selected from hydrogen, C₁₋₆ alkyl, C₅₋₆ aryl, C₁₋₆heteroaryl, C₂₋₁₀ heterocyclyl, oxo (═O), C₃₋₈ cycloalkyl, halogen, OH,amino, and cyano;R₃ is selected from the group consisting of hydrogen, substituted orunsubstituted C₁₋₈ alkyl, and C₅₋₆ aryl;R₂ is selected from the group consisting of —OR₇, aniline, amino C₅₋₆aryl, and amino C₁₋₆ heteroaryl,wherein aniline, amino C₅₋₆ aryl, and amino C₁₋₆ heteroaryl, isoptionally substituted with one or more of the groups selected from C₁₋₈alkyl, halogen, OH, amino, and cyano;R₇ is selected from the group consisting of hydrogen, C₁₋₈ alkyl, C₅₋₆aryl, C₂₋₁₀ heterocyclyl and —COR₈, wherein R₈ is selected from thegroup consisting of C₁₋₈ alkyl, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₃₋₈cycloalkyl, and C₂₋₁₀ heterocyclyl.

In an embodiment of the present invention, there is provided a compoundof Formula I

their analogs, tautomeric forms, stereoisomers, polymorphs, solvates,intermediates, pharmaceutically acceptable salts, metabolites, andprodrugs thereof;whereinAr is selected from the group consisting of substituted or unsubstitutedC₅₋₆aryl, C₁₋₆ heteroaryl, and C₂₋₁₀ heterocyclyl with heteroatomsselected from N, O, S;W represents a bond or CR₄R₅, whereinR₄ and R₅ are independently selected from the group consisting ofhydrogen, substituted or unsubstituted C₁₋₈ alkyl, C₅₋₆ aryl, and C₁₋₆heteroaryl with heteroatoms selected from N, O, S;Y is a bond or is selected from the group consisting of substituted orunsubstituted C₁₋₈ alkyl, C₁₋₈ alkenyl, C₁₋₈ alkynyl, C₅₋₆ aryl, C₁₋₆heteroaryl, C₂₋₁₀ heterocyclyl, C₃₋₈ cycloalkyl, —CO—, and —CO—C₂₋₁₀heterocyclyl;wherein C₁₋₈ alkyl, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₂₋₁₀ heterocyclyl, C₃₋₈cycloalkyl, is optionally substituted with one or more of the groupsselected from hydrogen, C₁₋₆ alkyl, oxo (═O), C₃₋₈ cycloalkyl, halogen,OH, and cyano;Z represents a bond or is selected from the group consisting of C₁₋₈alkyl, C₁₋₈ alkenyl, C₁₋₈ alkynyl, C₇₋₁₂-alkylaryl, C₇₋₁₂-alkenylaryl,C₇₋₁₅-arylalkenyl, C₂₋₁₂-alkylheteroaryl, —CO—C₇₋₁₂ alkylaryl, —CO—C₇₋₁₂alkenylaryl, —CONR₆—C₁₋₈ alkyl, —NR₆CO—C₁₋₈ alkyl-, —NR₆—C₁₋₈ alkyl,—O—C₁₋₈ alkyl-, —CONR₆—C₅₋₆ aryl-, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₂₋₁₀heterocyclyl, —NR₆—CO—OC₁₋₈ alkyl, O—CO—NR₆—C₁₋₈ alkyl, —NR₆CO—C₅₋₆aryl-, —NR₆—C₅₋₆ aryl, —NR₆—C₁₋₆ heteroaryl, —C₁₋₈ alkyl-O—C₅₋₆ aryl,—O—C₅₋₆ aryl, O—C₁₋₆ heteroaryl, —NR₆—CO—OC₅₋₆ aryl, —CONR₆—C₇₋₁₂alkylaryl, —CONR₆—C₇₋₁₂ alkenylaryl, —SO₂—C₅₋₆ aryl, —SO₂—C₇₋₁₂alkylaryl, —NR₆SO₂—C₇₋₁₂ alkylaryl, C₁₋₈ alkyl-CONR₆—C₅₋₆ aryl, andO—CO—NR₆—C₅₋₆ aryl;R₆ is selected from the group consisting of hydrogen, C₁₋₈ alkyl, C₁₋₆haloalkyl, C₃₋₈ cycloalkyl, C₅₋₆ aryl, and C₁₋₆ heteroaryl, withheteroatoms selected from N, O, S;R₁ is selected from the group consisting of hydrogen, halogen hydroxy,nitro, cyano, azido, nitroso, oxo (═O), thioxo (═S), —SO₂—, amino,hydrazino, formyl, C₁₋₈ alkyl, C₁₋₈ haloalkyl, C₁₋₈ alkoxy, C₁₋₈haloalkoxy, C₇₋₁₂ arylalkoxy, C₃₋₈ cycloalkyl, C₃₋₈ cycloalkyloxy, C₅₋₆aryl, C₂₋₁₀ heterocyclyl, C₁₋₆ heteroaryl, alkylamino, —COOR_(a),—C(O)R_(b), —C(S)R_(a), —C(O)NR_(a)R_(b), —C(S)NR_(a)R_(b),—NR_(a)C(O)NR_(b)R_(c), NR_(a)C(S)NR_(b)R_(c), —N(R_(a))SOR_(b),—N(R_(a))SO₂R_(b), —NR_(a)C(O)OR_(b), —NR_(a)R_(b), —NR_(a)C(O)R_(b)—,—NR_(a)C(S)R_(b)—, —SONR_(a)R_(b)—, —SO₂NR_(a)R_(b)—, —OR_(a),—OR_(a)C(O)OR_(b)—, —OC(O)NR_(a)R_(b), OC(O)R_(a), —OC(O)NR_(a)R_(b)—,—R_(a)NR_(b)R_(c), —R_(a)OR_(b)—, —SR_(a), —SOR_(a) and —SO₂R_(a),wherein R_(a), R_(b) and R_(c) is independently selected from the groupconsisting of hydrogen, C₁₋₈ alkyl, C₃₋₈ cycloalkyl, C₅₋₆ aryl, C₇₋₁₅arylalkyl, C₂₋₁₀ heterocyclyl, C₁₋₆ heteroaryl, and C₂₋₁₂heteroarylalkyl with heteroatoms selected from N, O, S;wherein C₇₋₁₂ arylalkoxy, C₁₋₈ alkyl, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₂₋₁₀heterocyclyl, C₃₋₈ cycloalkyl, is optionally substituted with one ormore of the groups selected from hydrogen, C₁₋₆ alkyl, C₅₋₆ aryl, C₁₋₆heteroaryl, C₂₋₁₀ heterocyclyl, oxo (═O), C₃₋₈ cycloalkyl, halogen, OH,amino, and cyano;R₃ is selected from the group consisting of hydrogen, substituted orunsubstituted C₁₋₈ alkyl, and C₅₋₆ aryl;R₂ is selected from the group consisting of —OR₇, aniline, amino C₅₋₆aryl, and amino C₁₋₆ heteroaryl,wherein aniline, amino C₅₋₆ aryl, and amino C₁₋₆ heteroaryl, isoptionally substituted with one or more of the groups selected from C₁₋₈alkyl, halogen, OH, amino, and cyano;R₇ is selected from the group consisting of hydrogen, C₁₋₈ alkyl, C₅₋₆aryl, C₂₋₁₀ heterocyclyl and —COR₈, wherein R₈ is selected from thegroup consisting of C₁₋₈ alkyl, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₃₋₈cycloalkyl, and C₂₋₁₀ heterocyclyl.

In an embodiment of the present invention, there is provided a compoundof Formula I

their analogs, tautomeric forms, stereoisomers, polymorphs, solvates,intermediates, pharmaceutically acceptable salts, metabolites, andprodrugs thereof;whereinAr is selected from the group consisting of substituted or unsubstitutedC₅₋₆aryl, C₁₋₆ heteroaryl, and C₂₋₁₀ heterocyclyl with heteroatomsselected from N, O, S;W represents a bond or CR₄R₅, whereinR₄ and R₅ are independently selected from the group consisting ofhydrogen, substituted or unsubstituted C₁₋₈ alkyl, C₅₋₆ aryl, and C₁₋₆heteroaryl with heteroatoms selected from N, O, S;Y is a bond or is selected from the group consisting of substituted orunsubstituted C₁₋₈ alkyl, C₁₋₈ alkenyl, C₁₋₈ alkynyl, C₅₋₆ aryl, C₁₋₆heteroaryl, C₂₋₁₀ heterocyclyl, C₃₋₈ cycloalkyl, —CO—, and —CO—C₂₋₁₀heterocyclyl;wherein C₁₋₈ alkyl, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₂₋₁₀ heterocyclyl, C₃₋₈cycloalkyl, is optionally substituted with one or more of the groupsselected from hydrogen, C₁₋₆ alkyl, oxo (═O), C₃₋₈ cycloalkyl, halogen,OH, and cyano;Z represents a bond or is selected from the group consisting of C₁₋₈alkyl, C₁₋₈ alkenyl, C₁₋₈ alkynyl, C₇₋₁₂-alkylaryl, C₇₋₁₂-alkenylaryl,C₇₋₁₅-arylalkenyl, C₂₋₁₂-alkylheteroaryl, —CO—C₇₋₁₂ alkylaryl, —CO—C₇₋₁₂alkenylaryl, —CONR₆—C₁₋₈ alkyl, —NR₆CO—C₁₋₈ alkyl-, —NR₆—C₁₋₈ alkyl,—O—C₁₋₈ alkyl-, —CONR₆—C₅₋₆ aryl-, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₂₋₁₀heterocyclyl, —CO—C₂₋₁₀ heterocyclyl, —NR₆—CO—OC₁₋₈ alkyl, O—CO—NR₆—C₁₋₈alkyl, —NR₆CO—C₅₋₆ aryl-, —NR₆—C₅₋₆ aryl, —NR₆—C₁₋₆ heteroaryl, —C₁₋₈alkyl-O—C₅₋₆ aryl, —O—C₅₋₆ aryl, O—C₁₋₆ heteroaryl, —NR₆—CO—OC₅₋₆ aryl,—CONR₆—C₇₋₁₂ alkenylaryl, —SO₂—C₅₋₆ aryl, —SO₂—C₇₋₁₂ alkylaryl,—NR₆SO₂—C₇₋₁₂ alkylaryl, C₁₋₈ alkyl-CONR₆—C₅₋₆ aryl, and O—CO—NR₆—C₅₋₆aryl;R₆ is selected from the group consisting of hydrogen, C₁₋₈ alkyl, C₁₋₆haloalkyl, C₃₋₈ cycloalkyl, C₅₋₆ aryl, and C₁₋₆ heteroaryl, withheteroatoms selected from N, O, S;R₁ is selected from the group consisting of hydrogen, halogen hydroxy,nitro, cyano, azido, nitroso, oxo (═O), thioxo (═S), —SO₂—, amino,hydrazino, formyl, C₁₋₈ alkyl, C₁₋₈ haloalkyl, C₁₋₈ alkoxy, C₁₋₈haloalkoxy, C₇₋₁₂ arylalkoxy, C₃₋₈ cycloalkyl, C₃₋₈ cycloalkyloxy, C₅₋₆aryl, C₂₋₁₀ heterocyclyl, C₁₋₆ heteroaryl, alkylamino, —COOR_(a),—C(O)R_(b), —C(S)R_(a), —C(O)NR_(a)R_(b), —C(S)NR_(a)R_(b),—NR_(a)C(O)NR_(b)R_(c), NR_(a)C(S)NR_(b)R_(c), —N(R_(a))SOR_(b),—N(R_(a))SO₂R_(b), —NR_(a)C(O)OR_(b), —NR_(a)R_(b), —NR_(a)C(O)R_(b)—,—NR_(a)C(S)R_(b)—, —SONR_(a)R_(b)—, —SO₂NR_(a)R_(b)—, —OR_(a),—OR_(a)C(O)OR_(b)—, —OC(O)NR_(a)R_(b), OC(O)R_(a), —OC(O)NR_(a)R_(b)—,—R_(a)NR_(b)R_(c), —R_(a)OR_(b)—, —SR_(a), —SOR_(a) and —SO₂R_(a),wherein R_(a), R_(b) and R_(c) is independently selected from the groupconsisting of hydrogen, C₁₋₈ alkyl, C₃₋₈ cycloalkyl, C₅₋₆ aryl, C₇₋₁₅arylalkyl, C₂₋₁₀ heterocyclyl, C₁₋₆ heteroaryl, and C₂₋₁₂heteroarylalkyl with heteroatoms selected from N, O, S;wherein C₇₋₁₂ arylalkoxy, C₁₋₈ alkyl, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₂₋₁₀heterocyclyl, C₃₋₈ cycloalkyl, is optionally substituted with one ormore of the groups selected from hydrogen, C₁₋₆ alkyl, C₅₋₆ aryl, C₁₋₆heteroaryl, C₂₋₁₀ heterocyclyl, oxo (═O), C₃₋₈ cycloalkyl, halogen, OH,amino, and cyano;R₃ is selected from the group consisting of hydrogen, substituted orunsubstituted C₁₋₈ alkyl, and C₅₋₆ aryl;R₂ is selected from the group consisting of —OR₇, aniline, amino C₅₋₆aryl, and amino C₁₋₆ heteroaryl,wherein aniline, amino C₅₋₆ aryl, and amino C₁₋₆ heteroaryl, isoptionally substituted with one or more of the groups selected from C₁₋₈alkyl, halogen, OH, amino, and cyano;R₇ is selected from the group consisting of hydrogen, C₁₋₈ alkyl, C₅₋₆aryl, C₂₋₁₀ heterocyclyl and —COR₈, wherein R₈ is selected from thegroup consisting of C₁₋₈ alkyl, C₅₋₆ aryl, C₁₋₆ heteroaryl, C₃₋₈cycloalkyl, and C₂₋₁₀ heterocyclyl.

According to an embodiment, the present disclosure relates to a compoundof Formula I or its stereoisomers, pharmaceutically acceptable salts,complexes, hydrates, solvates, tautomers, polymorphs, racemic mixtures,optically active forms and pharmaceutically active derivative thereof,which is selected from a group consisting of:

-   1)    (E)3(4(((2(4-Cyclopropylphenyl)cyclopropyl)amino)methyl)phenyl)-N-hydroxyacrylamide    TFA salt-   2)    (E)-3-(4-{[2-(4-Fluoro-phenyl)-cyclopropylamino]-methyl}-phenyl)-N-hydroxy-acrylamide    TFA salt-   3)    (E)-3-(4-(((2-(4-((4-Fluorobenzyl)oxy)phenyl)cyclopropyl)amino)methyl)phenyl)-N-hydroxyacrylamideTFA    salt-   4)    (E)-N-hydroxy-3-(4-(4-(((2-phenylcyclopropyl)amino)methyl)piperidin-1-yl)phenyl)    acrylamideTFA salt-   5)    (E)-3-(4-(((2-(4′-Chloro-[1,1′-biphenyl]-4-yl)cyclopropyl)amino)methyl)phenyl)-N-hydroxyacrylamideTFA    salt-   6)    (E)-3-(4-(((2-(4-(3,5-Dimethylisoxazol-4-yl)phenyl)cyclopropyl)amino)methyl)phenyl)-N-hydroxyacrylamide.    TFA salt-   7)    (E)-N-hydroxy-3-(4-(((2-(4-(pyrimidin-5-yl)phenyl)cyclopropyl)amino)methyl)phenyl)    acrylamide TFA salt-   8)    2-(4-(((2-(4-Fluorophenyl)cyclopropyl)amino)methyl)piperidin-1-yl)-N-hydroxy    pyrimidine-5-carboxamide TFA salt-   9)    2-[4-(2-Phenyl-cyclopropylamino)-piperidin-1-yl]-pyrimidine-5-carboxylicacid    hydroxyamide TFA salt-   10)    2-{4-[2-(4-Fluorophenyl)-cyclopropylamino]-piperidin-1-yl}-pyrimidine-5-carboxylic    acid hydroxyamide TFA salt-   11)    2-(4-(((2-(4-((4-Fluorobenzyl)oxy)phenyl)cyclopropyl)amino)methyl)piperidin-1-yl)-N-hydroxypyrimidine-5-carboxamideTFA    salt-   12)    2-(4-((2-(4-((4-Fluorobenzyl)oxy)phenyl)cyclopropyl)amino)piperidin-1-yl)-N-hydroxypyrimidine-5-carboxamideTFA    salt-   13)    2-(4-((2-(4′-Chloro-[1,1′-biphenyl]-4-yl)cyclopropyl)amino)piperidin-1-yl)-N-hydroxypyrimidine-5-carboxamideTFA    salt-   14)    2-(4-(((2-(4′-Chloro-[1,1′-biphenyl]-4-yl)cyclopropyl)amino)methyl)piperidin-1-yl)-N-hydroxypyrimidine-5-carboxamide    TFA salt-   15)    2-(4-(((2-(4′-Fluoro-[1,1′-biphenyl]-4-yl)cyclopropyl)amino)methyl)piperidin-1-yl)-N-hydroxypyrimidine-5-carboxamide    TFA salt-   16)    2-(4-(((2-(4-(3,5-Dimethylisoxazol-4-yl)phenyl)cyclopropyl)amino)methyl)piperidin-1-yl)-N-hydroxypyrimidine-5-carboxamide.    TFA salt-   17)    N-hydroxy-2-(4-(((2-(4-(pyrimidin-5-yl)phenyl)cyclopropyl)amino)methyl)    piperidin-1-yl)pyrimidine-5-carboxamide.TFA salt-   18)    N-hydroxy-2-(4-(((2-(4-methoxyphenyl)cyclopropyl)amino)methyl)piperidin-1-yl)pyrimidine-5-carboxamideTFA    salt-   19)    N-hydroxy-2-(4-((2-(4-methoxyphenyl)cyclopropyl)amino)piperidin-1-yl)pyrimidine-5-carboxamide    TFA salt-   20)    2-(4-((((1R,2S)-2-(4-Fluorophenyl)cyclopropyl)amino)methyl)piperidin-1-yl)-N-hydroxypyrimidine-5-carboxamide    TFA salt-   21)    2-(4-((((1S,2R)-2-(4-Fluorophenyl)cyclopropyl)amino)methyl)piperidin-1-yl)-N-hydroxypyrimidine-5-carboxamide    TFA salt-   22)    4-(4-(((2-(4-Fluorophenyl)cyclopropyl)amino)methyl)piperidin-1-yl)-N-hydroxybenzamide    TFA salt-   23)    N-hydroxy-2-(2-(((2-phenylcyclopropyl)amino)methyl)-5,6-dihydroimidazo[1,2-a]pyrazin-7(8H)-yl)pyrimidine-5-carboxamide    TFA salt-   24)    N-hydroxy-2-(2-(((2-(4-methoxyphenyl)cyclopropyl)amino)methyl)-5,6-dihydroimidazo[1,2-a]pyrazin-7(8H)-yl)pyrimidine-5-carboxamide    TFA salt-   25)    2-(2-(((2-(4-Fluorophenyl)cyclopropyl)amino)methyl)-5,6-dihydroimidazo[1,2-a]pyrazin-7(8H)-yl)-N-hydroxypyrimidine-5-carboxamide    TFA salt-   26)    3-(((2-(4-Bromophenyl)cyclopropyl)amino)methyl)-N-hydroxybenzamide    TFA salt-   27) N-hydroxy-3-(((2-phenylcyclopropyl)amino)methyl)benzamide TFA    salt-   28) N-hydroxy-4-(((2-phenylcyclopropyl)amino)methyl)benzamide TFA    salt-   29) N-hydroxy-6-((2-phenylcyclopropyl)amino)hexanamide TFA salt-   30)    4-(3-((2-(4-Fluorophenyl)cyclopropyl)amino)propyl)-N-hydroxybenzamide    TFA salt-   31)    N-(6-Hydroxycarbamoyl-hexyl)-4-[(2-phenyl-cyclopropylamino)-methyl]-benzamide    TFA salt-   32)    4-(((2-(4-Fluorophenyl)cyclopropyl)amino)methyl)-N-(7-(hydroxyamino)-7-oxoheptyl)benzamide    TFA salt-   33) 4-(2-Phenyl-cyclopropylamino)-cyclohexanecarboxylic acid    hydroxyamide TFA salt-   34)    (1S,4R)—N-hydroxy-4-((1S)-1-((2-phenylcyclopropyl)amino)ethyl)cyclohexanecarboxamide    TFA salt-   35)    N-hydroxy-4-((4-(((2-(4-(1-methyl-6-oxo-1,6-dihydropyridin-3-yl)phenyl)cyclopropyl)amino)methyl)piperidin-1-yl)methyl)benzamide    TFA Salt-   36)    N-Hydroxy-4-{4-[(2-phenyl-cyclopropylamino)-methyl]-piperidin-1-ylmethyl}-benzamide    TFA salt-   37)    4-((4-(((2-(4-(3,5-Dimethylisoxazol-4-yl)phenyl)cyclopropyl)amino)methyl)piperidin-1-yl)    methyl)-N-hydroxybenzamide-   TFA salt-   38)    N-hydroxy-4-((4-(((2-(4-(pyrimidin-5-yl)phenyl)cyclopropyl)amino)methyl)piperidin-1-yl)methyl)benzamide    TFA salt-   39)    6-((4-(((2-(4-(3,5-Dimethylisoxazol-4-yl)phenyl)cyclopropyl)amino)methyl)piperidin-1-yl)methyl)-N-hydroxynicotinamide-   TFA salt-   40)    N-hydroxy-4-((4-(((2-phenylcyclopropyl)amino)methyl)-1H-pyrazol-1-yl)methyl)    benzamide TFA salt-   41)    N-hydroxy-4-((4-(((2-phenylcyclopropyl)amino)methyl)-1H-1,2,3-triazol-1-yl)    methyl)benzamide TFA salt-   42)    N-hydroxy-4-(2-(4-(((2-phenylcyclopropyl)amino)methyl)piperidin-1-yl)ethyl)benzamide    TFA salt-   43)    N-hydroxy-4-(3-(4-(((2-phenylcyclopropyl)amino)methyl)piperidin-1-yl)propyl)benzamide    TFA salt-   44)    N-hydroxy-4-(3-(4-((2-phenylcyclopropyl)amino)piperidin-1-yl)propyl)benzamideTFA    salt-   45) N-hydroxy-4-(3-(4-((methyl (2-phenylcyclopropyl) amino) methyl)    piperidin-1-yl) propyl)benzamide TFA salt-   46)    N-hydroxy-4-(3-(6-((2-phenylcyclopropyl)amino)-2-azaspiro[3.3]heptan-2-yl)propyl)    benzamide TFA salt-   47)    4-[3-(4-{[2-(4-Fluorophenyl)-cyclopropylamino]-methyl}-piperidin-1-yl)-propyl]-N-hydroxy-benzamide    TFA salt-   48)    4-(3-(3-(((2-(4-Fluorophenyl)cyclopropyl)amino)methyl)azetidin-1-yl)propyl)-N-hydroxy    benzamide TFA salt-   49)    4-(3-(4-(((2-(3-Fluorophenyl)cyclopropyl)amino)methyl)piperidin-1-yl)propyl)-N-hydroxy    benzamide TFA salt-   50)    4-(3-(4-(((2-(3,4-Difluorophenyl)cyclopropyl)amino)methyl)piperidin-1-yl)propyl)-N-hydroxybenzamide    TFA salt-   51)    N-hydroxy-4-(3-(4-(((2-(4-methoxyphenyl)cyclopropyl)amino)methyl)piperidin-1-yl)propyl)benzamide    TFA salt-   52)    N-hydroxy-4-(3-(4-(((2-(4-(morpholine-4-carbonyl)phenyl)cyclopropyl)amino)methyl)piperidin-1-yl)propyl)benzamide    TFA salt-   53)    N-hydroxy-4-(3-(4-(((2-(4-(morpholine-4-carbonyl)phenyl)cyclopropyl)amino)methyl)piperidin-1-yl)propyl)benzamide    TFA salt-   54)    N-hydroxy-4-(3-(4-(((2-(4-(piperidine-1-carbonyl)phenyl)cyclopropyl)amino)methyl)piperidin-1-yl)propyl)benzamide    TFA salt-   55)    N-(2-(Dimethylamino)ethyl)-4-(2-(((1-(3-(4-(hydroxycarbamoyl)phenyl)propyl)piperidin-4-yl)methyl)amino)cyclopropyl)benzamide    TFA salt-   56)    4-(3-(4-(((2-(4′-Chloro-[1,1′-biphenyl]-4-yl)cyclopropyl)amino)methyl)piperidin-1-yl)propyl)-N-hydroxybenzamide    TFA salt-   57)    4-(3-(4-(((2-(4′-Fluoro-[1,1′-biphenyl]-4-yl)cyclopropyl)amino)methyl)piperidin-1-yl)propyl)-N-hydroxybenzamide    TFA salt-   58)    4-(3-(3-(((2-(4′-Fluoro-[1,1′-biphenyl]-4-yl)cyclopropyl)amino)methyl)azetidin-1-yl)    propyl)-N-hydroxybenzamide TFA salt-   59)    4-(3-(4-(((2-(4′-Cyano-[1,1′-biphenyl]-4-yl)cyclopropyl)amino)methyl)piperidin-1-yl)propyl)-N-hydroxybenzamideTFA    salt-   60)    N-hydroxy-4-(3-(4-(((2-(4-(1-methyl-2-oxo-1,2-dihydropyridin-4-yl)phenyl)cyclopropyl)amino)methyl)piperidin-1-yl)propyl)benzamide.    TFA salt-   61)    N-hydroxy-4-(3-(4-(((2-(4-(pyrimidin-5-yl)phenyl)cyclopropyl)amino)methyl)piperidin-1-yl)propyl)benzamide    TFA salt-   62)    N-hydroxy-4-(3-(4-(((2-(4-(1-methyl-1H-pyrazol-4-yl)phenyl)cyclopropyl)amino)    methyl)piperidin-1-yl) propyl) benzamide TFA salt-   63)    N-hydroxy-4-(3-(3-(((2-(4-(1-methyl-1H-pyrazol-4-yl)phenyl)cyclopropyl)amino)    methyl) azetidin-1-yl)propyl)benzamide-   64)    4-(3-(4-(((2-(4-(3,5-Dimethylisoxazol-4-yl)phenyl)cyclopropyl)amino)methyl)piperidin-1-yl)propyl)-N-hydroxybenzamide    TFA salt-   65)    3-(3-(3-(((2-(4-(3,5-Dimethylisoxazol-4-yl)phenyl)cyclopropyl)amino)methyl)azetidin-1-yl)propyl)-N-hydroxybenzamideTFA    salt-   66)    N-hydroxy-4-(3-(4-(((2-(4-(6-(trifluoromethyl)pyridin-3-yl)phenyl)cyclopropyl)amino)methyl)piperidin-1-yl)propyl)benzamideTFA    salt-   67)    N-hydroxy-4-(3-(4-(((2-(1-isopropyl-1H-pyrazol-4-yl)cyclopropyl)amino)methyl)piperidin-1-yl)propyl)benzamideTFA    salt-   68)    N-hydroxy-4-(3-(4-(((2-(1-phenyl-1H-pyrazol-4-yl)cyclopropyl)amino)methyl)piperidin-1-yl)propyl)benzamideTFA    salt-   69)    N-hydroxy-4-(3-(4-(((2-(2-methylthiazol-5-yl)cyclopropyl)amino)methyl)piperidin-1-yl)propyl)benzamideTFA    salt-   70)    N-hydroxy-4-(3-(4-(((2-(pyridin-3-yl)cyclopropyl)amino)methyl)piperidin-1-yl)propyl)    benzamideTFA salt-   71)    N-hydroxy-4-(3-(2-(((2-(4-methoxyphenyl)cyclopropyl)amino)methyl)-5,6-dihydroimidazo[1,2-a]pyrazin-7(8H)-yl)propyl)benzamide    TFA salt-   72)    4-(3-(2-(((2-(4-Fluorophenyl)cyclopropyl)amino)methyl)-5,6-dihydroimidazo[1,2-a]    pyrazin-7(8H)-yl)propyl)-N-hydroxybenzamide TFA salt-   73)    4-(3-(4-(((2-(3,4-Difluorophenyl)cyclopropyl)amino)methyl)-1H-imidazol-1-yl)    propyl)-N-hydroxybenzamide TFA salt-   74)    N-hydroxy-4-(3-(4-(((2-phenylcyclopropyl)amino)methyl)-1H-imidazol-1-yl)propyl)    benzamide TFA salt-   75)    N-hydroxy-4-(3-(4-(((2-phenylcyclopropyl)amino)methyl)-1H-imidazol-1-yl)propyl)    benzamide-   76)    N-hydroxy-4-(3-(4-(((2-phenylcyclopropyl)amino)methyl)-1H-pyrazol-1-yl)propyl)    benzamide TFA salt-   77)    N-hydroxy-4-(3-(4-(((2-phenylcyclopropyl)amino)methyl)-1H-1,2,3-triazol-1-yl)propyl)benzamide    TFA salt-   78)    4-(3-(6-(((2-(4-Fluorophenyl)cyclopropyl)amino)methyl)-3,4-dihydroisoquinolin-2-(1H)-yl)propyl)-N-hydroxybenzamide    TFA salt-   79)    4-((7-(((2-(4-Fluorophenyl)cyclopropyl)amino)methyl)-3,4-dihydroisoquinolin-2(1H)-yl)methyl)-N-hydroxybenzamide    TFA salt-   80)    4-((2-(((2-(4-Fluorophenyl)cyclopropyl)amino)methyl)-5,6-dihydroimidazo[1,2-a]pyrazin-7    (8H)-yl)methyl)-N-hydroxybenzamide TFA salt-   81)    N-hydroxy-4-(3-(4(((2-(1,3,3,-trimethyl-2-oxoindoline-5-yl)cyclopropyl)amino)methyl)    piperidine-1-yl)propyl)benzamide TFA salt-   82)    N-hydroxy-4-(3-oxo-3-(4-(((2-phenylcyclopropyl)amino)methyl)piperidin-1-yl)propyl)benzamide    TFA salt-   83)    N-hydroxy-4-(3-oxo-3-(4-((2-phenylcyclopropyl)amino)piperidin-1-yl)propyl)benzamide    TFA salt-   84)    N-hydroxy-4-(2-oxo-2-(4-(((2-phenylcyclopropyl)amino)methyl)piperidin-1-yl)ethyl)    benzamide TFA Salt-   84A.    N-hydroxy-4-(2-oxo-2-(4-((((1R,2S)-2-phenylcyclopropyl)amino)methyl)piperidin-1-yl)    ethyl)benzamide-   84B.    N-hydroxy-4-(2-oxo-2-(4-((((1S,2R)-2-phenylcyclopropyl)amino)methyl)piperidin-1-yl)    ethyl)benzamide-   85)    N-hydroxy-4-((4-(((2-phenylcyclopropyl)amino)methyl)piperidin-1-yl)sulfonyl)    benzamide TFA salt-   86)    N-hydroxy-4-((N-(2-(4-(((2-phenylcyclopropyl)amino)methyl)piperidin-1-yl)ethyl)    sulfamoyl)methyl)benzamideTFA salt-   87)    4-(N-(2-(4-(((2-(4-fluorophenyl)cyclopropyl)amino)methyl)piperidin-1-yl)ethyl)    sulfamoyl)-N-hydroxybenzamide-   88)    N-hydroxy-4-(2-((4-(((2-phenylcyclopropyl)amino)methyl)piperidin-1-yl)sulfonyl)ethyl)    benzamide TFA salt-   89)    N-hydroxy-N4-(2-(4-(((2-phenylcyclopropyl)amino)methyl)piperidin-1-yl)ethyl)    terephthalamideTFA salt-   90)    N1-(2-(4-(((2-(3,4-difluorophenyl)cyclopropyl)amino)methyl)piperidin-1-yl)ethyl)-N4-hydroxyterephthalamide    TFA salt-   91)    N-hydroxy-4-((4-(2-((2-phenylcyclopropyl)amino)acetyl)piperazin-1-yl)methyl)benzamide    TFA salt-   92)    N-hydroxy-4-(3-oxo-3-(4-(2-((2-phenylcyclopropyl)amino)acetyl)piperazin-1-yl)propyl)benzamide    TFA salt-   93)    N-hydroxy-4-(3-(1-(2-((2-phenylcyclopropyl)amino)acetyl)piperidin-4-yl)propyl)benzamide    TFA salt-   94)    N-hydroxy-4-(3-(2-oxo-4-(((2-phenylcyclopropyl)amino)methyl)piperidin-1-yl)    propyl)benzamide TFA salt-   95) N-hydroxy-4-(2-((2-phenylcyclopropyl)amino)ethoxy)benzamide TFA    salt-   96)    6-(2-(4-(((2-(4-fluorophenyl)cyclopropyl)amino)methyl)piperidin-1-yl)ethoxy)-N-hydroxynicotinamide    TFA salt-   97)    N-hydroxy-6-(2-(4-(((2-phenylcyclopropyl)amino)methyl)piperidin-1-yl)ethoxy)nicotinamide    TFA salt-   98)    6-(2-(4-(((2-(4′-Fluoro-[1,1′-biphenyl]-4-yl)cyclopropyl)amino)methyl)piperidin-1-yl)    ethoxy)-N-hydroxynicotinamide TFA salt-   99)    N-hydroxy-4-(2-(4-(((2-phenylcyclopropyl)amino)methyl)piperidin-1-yl)ethoxy)benzamide    TFA salt-   100)    N-hydroxy-4-(3-(4-(((2-phenylcyclopropyl)amino)methyl)piperidin-1-yl)propoxy)benzamide    TFA salt-   101) N-hydroxy-4-(3-((2-phenylcyclopropyl)amino)propoxy)benzamide    TFA salt-   102)    2-((2-(4-(((2-(4-Fluorophenyl)cyclopropyl)amino)methyl)piperidin-1-yl)ethyl)amino)-N-hydroxypyrimidine-5-carboxamide    TFA salt-   103)    5-(2-((2-(4-Fluorophenyl)cyclopropyl)amino)acetyl)-N-hydroxy-4,5,6,7-tetrahydro    thieno[3,2-c]pyridine-2-carboxamide TFA salt-   103A)    5-(2-(((1R,2S)-2-(4-Fluorophenyl)cyclopropyl)amino)acetyl)-N-hydroxy-4,5,6,7-tetrahydrothieno[3,2-c]pyridine-2-carboxamide    TFA salt-   103B)    5-(2-(((1S,2R)-2-(4-Fluorophenyl)cyclopropyl)amino)acetyl)-N-hydroxy-4,5,6,7-tetrahydrothieno[3,2-c]pyridine-2-carboxamide    TFA salt-   104)    2-(2-((2-(4-Fluorophenyl)cyclopropyl)amino)acetyl)-N-hydroxy-1,2,3,4-tetrahydro    isoquinoline-7-carboxamide TFA salt-   104A)    2-(2-(((1S,2R)-2-(4-Fluorophenyl)cyclopropyl)amino)acetyl)-N-hydroxy-1,2,3,4-tetrahydroisoquinoline-7-carboxamide    TFA salt-   104B)    2-(2-(((1R,2S)-2-(4-Fluorophenyl)cyclopropyl)amino)acetyl)-N-hydroxy-1,2,3,4-tetrahydroisoquinoline-7-carboxamide    TFA salt-   105)    5-(4-((2-(4-Fluorophenyl)cyclopropyl)amino)butanoyl)-N-hydroxy-4,5,6,7-tetrahydro    thieno[3,2-c]pyridine-2-carboxamide TFA salt-   106)    5-(4-(4-(((2-(4-Fluorophenyl)cyclopropyl)amino)methyl)piperidin-1-yl)butanoyl)-N-hydroxy-4,5,6,7-tetrahydrothieno[3,2-c]pyridine-2-carboxamide    TFA salt-   107)    2-(4-((2-(4-Fluorophenyl)cyclopropyl)amino)butanoyl)-N-hydroxy-1,2,3,4-tetrahydro    isoquinoline-7-carboxamide TFA salt-   108)    2-(4-((2-(4-Fluorophenyl)cyclopropyl)amino)butanoyl)-N-hydroxyisoindoline-5-carboxamide    TFA salt-   109)    N-hydroxy-2-(4-(4-(((2-phenylcyclopropyl)amino)methyl)piperidin-1-yl)butanoyl)    isoindoline-5-carboxamide TFA salt-   110)    N-hydroxy-2-(3-(4-(((2-phenylcyclopropyl)amino)methyl)piperidin-1-yl)propyl)    thiazole-4-carboxamide TFA salt-   111)    2-(3-(4-(((2-(4′-Fluoro-[1,1′-biphenyl]-4-yl)cyclopropyl)amino)methyl)piperidin-1-yl)propyl)-N-hydroxythiazole-4-carboxamide    TFA salt-   112)    N-hydroxy-2-(3-(4-(((2-phenylcyclopropyl)amino)methyl)piperidin-1-yl)propyl)    thiazole-5-carboxamide TFA salt-   113)    N-hydroxy-2-(3-(4-(((2-phenylcyclopropyl)amino)methyl)piperidin-1-yl)propyl)    oxazole-4-carboxamide TFA salt-   114)    (E)-N-hydroxy-4-(3-oxo-3-(4-(((2-phenylcyclopropyl)amino)methyl)piperidin-1-yl)    prop-1-en-1-yl)benzamide TFA salt-   114A)    N-hydroxy-4-((E)-3-oxo-3-(4-((((1R,2S)-2-phenylcyclopropyl)amino)methyl)    piperidin-1-yl)prop-1-en-1-yl)benzamide TFA salt-   114B)    N-hydroxy-4-((E)-3-oxo-3-(4-((((1S,2R)-2-phenylcyclopropyl)amino)methyl)    piperidin-1-yl)prop-1-en-1-yl)benzamide TFA salt-   115)    4-((E)-3-(4-((((1S,2R)-2-(4-Fluorophenyl)cyclopropyl)amino)methyl)    piperidin-1-yl)-3-oxoprop-1-en-1-yl)-N-hydroxybenzamide TFA salt-   115A)    4-((E)-3-(4-((((1S,2R)-2-(4-Fluorophenyl)cyclopropyl)amino)methyl)    piperidin-1-yl)-3-oxoprop-1-en-1-yl)-N-hydroxybenzamide TFA salt-   116)    (E)-4-(3-(4-(((2-(4-(3,5-Dimethylisoxazol-4-yl)phenyl)cyclopropyl)amino)methyl)    piperidin-1-yl)-3-oxoprop-1-en-1-yl)-N-hydroxybenzamide TFA salt-   117)    (E)-N-hydroxy-4-(3-oxo-3-(4-(((2-(4-(pyrimidin-5-yl)phenyl)cyclopropyl)amino)    methyl)piperidin-1-yl)prop-1-en-1-yl)benzamide TFA salt-   118)    (E)-4-(3-(3-(((2-(4-Fluorophenyl)cyclopropyl)amino)methyl)azetidin-1-yl)-3-oxoprop-1-en-1-yl)-N-hydroxybenzamideTFA    salt-   119)    (E)-N-hydroxy-4-(3-(3-(((2-(4-(1-methyl-1H-pyrazol-4-yl)phenyl)cyclopropyl)amino)methyl)azetidin-1-yl)-3-oxoprop-1-en-1-yl)benzamide    TFA salt-   120)    (E)-N-(2-aminophenyl)-3-(4-(((2-(4-fluorophenyl)cyclopropyl)amino)methyl)phenyl)acrylamide    TFA salt-   121)    N-(2-aminophenyl)-4-(3-(4-(((2-phenylcyclopropyl)amino)methyl)piperidin-1-yl)propyl)benzamide    TFA salt-   122)    N-(2-aminophenyl)-4-(3-(4-(((2-(4-fluorophenyl)cyclopropyl)amino)methyl)piperidin-1-yl)propyl)benzamide    TFA salt-   123)    N-(2-aminophenyl)-4-(3-(4-(((2-(4-methoxyphenyl)cyclopropyl)amino)methyl)piperidin-1-yl)propyl)benzamide    TFA salt-   124)    N-(2-aminophenyl)-4-(3-(4-(((2-(3,4-difluorophenyl)cyclopropyl)amino)methyl)    piperidin-1-yl)propyl)benzamide TFA salt-   125)    N-(2-aminophenyl)-4-(3-(4-(((2-(4-(piperidine-1-carbonyl)phenyl)cyclopropyl)amino)methyl)piperidin-1-yl)propyl)benzamide    TFA salt-   126)    N-(2-aminophenyl)-4-(3-(3-(((2-(4-fluorophenyl)cyclopropyl)amino)methyl)azetidin-1-yl)    propyl)benzamide TFA salt-   127)    N-(2-aminophenyl)-4-(3-(6-((2-phenylcyclopropyl)amino)-2-azaspiro[3.3]heptan-2-yl)propyl)benzamide    TFA salt-   128)    N-(2-aminophenyl)-4-(3-(4-(((2-(1-isopropyl-1H-pyrazol-4-yl)cyclopropyl)amino)methyl)piperidin-1-yl)propyl)benzamide    TFA salt-   129)    N-(2-aminophenyl)-4-(3-(4-(((2-(1-phenyl-1H-pyrazol-4-yl)cyclopropyl)amino)methyl)piperidin-1-yl)propyl)benzamide    TFA salt-   130)    N-(2-aminophenyl)-4-(3-(4-(((2-(2-methylthiazol-5-yl)cyclopropyl)amino)methyl)    piperidin-1-yl)propyl)benzamide TFA salt-   131)    N-(2-aminophenyl)-4-(3-(4-(((2-(pyridin-3-yl)cyclopropyl)amino)methyl)piperidin-1-yl)propyl)benzamide    TFA salt-   132)    N-(2-amino-5-fluorophenyl)-4-(3-(4-(((2-(4-fluorophenyl)cyclopropyl)amino)methyl)piperidin-1-yl)propyl)benzamide    TFA salt-   133)    N-(2-aminophenyl)-4-(3-oxo-3-(4-((2-phenylcyclopropyl)amino)piperidin-1-yl)propyl)benzamide    TFA salt-   134)    N-(2-aminophenyl)-4-(3-oxo-3-(4-(((2-phenylcyclopropyl)amino)methyl)piperidin-1-yl)propyl)benzamide    TFA salt-   135)    N-(2-aminophenyl)-4-(3-(4-(((2-(3,4-difluorophenyl)cyclopropyl)amino)methyl)-1H-imidazol-1-yl)propyl)benzamide    TFA salt-   136)    N-(2-aminophenyl)-4-(3-(4-(((2-phenylcyclopropyl)amino)methyl)-1H-imidazol-1-yl)propyl)benzamide    TFA salt-   137)    N-(2-aminophenyl)-4-(3-(4-(((2-phenylcyclopropyl)amino)methyl)-1H-1,2,3-triazol-1-yl)propyl)benzamide    TFA salt-   138)    N-(2-aminophenyl)-4-(3-(4-(((2-phenylcyclopropyl)amino)methyl)-1H-pyrazol-1-yl)propyl)benzamide    TFA salt-   139)    N-(2-aminophenyl)-4-(2-(4-(((2-phenylcyclopropyl)amino)methyl)piperidin-1-yl)    ethyl)benzamide TFA salt-   140)    N-(2-aminophenyl)-4-((4-((((1R,2S)-2-phenylcyclopropyl)amino)methyl)piperidin-1-yl)    methyl)benzamide TFA salt-   141)    N-(2-aminophenyl)-4-((4-(((2-(4-(1-methyl-6-oxo-1,6-dihydropyridin-3-yl)phenyl)    cyclopropyl)amino)methyl)piperidin-1-yl)methyl)benzamide TFA salt-   142)    N-(2-aminophenyl)-4-((4-(((2-(4-(1-methyl-1H-pyrazol-4-yl)phenyl)cyclopropyl)amino)methyl)piperidin-1-yl)methyl)benzamide    TFA salt-   143)    N-(2-aminophenyl)-4-((4-(((2-(4-(3,5-dimethylisoxazol-4-yl)phenyl)cyclopropyl)amino)    methyl)piperidin-1-yl)methyl)benzamide TFA salt-   144)    N-(2-aminophenyl)-4-((4-(((2-(4-(pyrimidin-5-yl)phenyl)cyclopropyl)amino)methyl)piperidin-1-yl)methyl)benzamide    TFA salt-   145)    N-(2-aminophenyl)-4-((4-(((2-phenylcyclopropyl)amino)methyl)-1H-pyrazol-1-yl)methyl)benzamideTFA    salt-   146)    N-(2-aminophenyl)-4-((4-(((2-phenylcyclopropyl)amino)methyl)-1H-1,2,3-triazol-1-yl)methyl)benzamideTFA    salt-   147)    N-(2-aminophenyl)-4-(2-(4-(((2-(4-fluorophenyl)cyclopropyl)amino)methyl)piperidin-1-yl)-2-oxoethyl)benzamide    TFA salt-   148) N-(2-aminophenyl)-4-(2-((2-(4-fluorophenyl) cyclopropyl)amino)    ethoxy) benzamide TFA salt-   149)    N-(2-aminophenyl)-6-(2-(4-(((2-(4-fluorophenyl)cyclopropyl)amino)methyl)piperidin-1-yl)ethoxy)nicotinamide    TFA salt-   150)    N-(-2-aminophenyl)-2-((2-4(((2-(4-flurophenyl)cyclopropyl)amino)methyl)piperdine-1-yl)ethyl)amino)pyrimidine-5-carboxamide    TFA salt-   151)    N-(2-aminophenyl)-5-((2-(4-fluorophenyl)cyclopropyl)glycyl)-4,5,6,7-tetrahydrothieno[3,2-c]pyridine-2-carboxamide    TFA salt-   152)    N-(2-aminophenyl)-2-(2-((2-(4-fluorophenyl)cyclopropyl)amino)acetyl)-1,2,3,4-tetrahydroisoquinoline-7-carboxamide    TFA salt-   153)    N-(2-aminophenyl)-2-(3-(4-(((2-phenylcyclopropyl)amino)methyl)piperidin-1-yl)propyl)oxazole-4-carboxamide    TFA salt-   154)    N-(2-aminophenyl)-2-(3-(4-(((2-phenylcyclopropyl)amino)methyl)piperidin-1-yl)propyl)thiazole-5-carboxamide    TFA salt-   155)    N-(2-aminophenyl)-4-((2-((2-(4-fluorophenyl)cyclopropyl)amino)acetamido)    methyl)benzamide TFA salt-   156)    (E)-N-(2-aminophenyl)-4-(3-(4-(((2-(4-fluorophenyl)cyclopropyl)amino)methyl)piperidin-1-yl)-3-oxoprop-1-en-1-yl)benzamide    TFA salt-   157)    (E)-N-(2-aminophenyl)-4-(3-(3-(((2-(4-fluorophenyl)cyclopropyl)amino)methyl)azetidin-1-yl)-3-oxoprop-1-en-1-yl)benzamide    TFA salt-   158)    N-(4-((2-aminophenyl)carbamoyl)benzyl)-4-(((2-(4-fluorophenyl)cyclopropyl)amino)methyl)piperidine-1-carboxamide    TFA salt-   159)    N-(2-aminophenyl)-4-(3-(2-oxo-4-(((2-phenylcyclopropyl)amino)methyl)piperidin-1-yl)propyl)benzamide    TFA salt-   160)    N-(2-aminophenyl)-4-((4-(((2-phenylcyclopropyl)amino)methyl)piperidin-1-yl)sulfonyl)    benzamide TFA salt-   161)    N-(2-aminophenyl)-4-(((4-(((2-phenylcyclopropyl)amino)methyl)piperidin-1-yl)    sulfonyl)methyl)benzamide TFA salt-   162)    N-(2-aminophenyl)-4-(2-((4-(((2-phenylcyclopropyl)amino)methyl)piperidin-1-yl)sulfonyl)ethyl)benzamide    TFA salt

In an embodiment, the invention relates to a process of preparation ofcompounds of Formula (I) or its tautomers, polymorphs, stereoisomers,prodrugs, solvate, co-crystals or pharmaceutically acceptable saltsthereof.

In another embodiment, the invention relates to a pharmaceuticalcomposition comprising a compound of Formula (I) or a pharmaceuticallyacceptable salt thereof of together with a pharmaceutically acceptablecarrier, optionally in combination with one or more other pharmaceuticalcompositions.

In yet another embodiment, the invention relates to the pharmaceuticalcomposition as described herein, wherein the composition is in the formselected from the group consisting of a tablet, capsule, powder, syrup,solution, aerosol, and suspension.

In an embodiment, the invention relates to the compound of Formula I ora pharmaceutically acceptable salt thereof for use in the manufacture ofa medicament for inhibiting LSD1 enzymes in a cell.

In another embodiment, the invention relates to A method of inhibitingLSD1 in a cell, comprising treating said cell with an effective amountof the compound of Formula I.

In yet another embodiment, the invention relates to a method of treatinga condition mediated by LSD1 comprising administering to a subjectsuffering from a condition mediated by LSD1, a therapeutically effectiveamount of the compound of Formula I or the pharmaceutical compositiondescribed herein.

In an embodiment, the invention relates to a compound of Formula I or apharmaceutically acceptable salt thereof for use in the manufacture of amedicament for inhibiting HDAC enzymes in a cell.

In another embodiment, the invention relates to a method of inhibitingHDAC in a cell comprising treating said cell with an effective amount ofthe compound of Formula I.

In yet another embodiment, the invention relates to a method of treatinga condition mediated by HDAC, comprising administering to a subjectsuffering from a condition mediated by HDAC, a therapeutically effectiveamount of the compound of Formula I or the pharmaceutical composition asdescribed herein.

In an embodiment, the invention relates to a compound of Formula I or apharmaceutically acceptable salt thereof for use in the manufacture of amedicament for inhibiting both LSD1 and HDAC enzymes in a cell.

In another embodiment, the invention relates to a method of inhibitingboth LSD1 and HDAC in a cell comprising treating said cell with aneffective amount of the compound of Formula I.

In yet another embodiment, the invention relates to a method of treatinga condition mediated by both LSD1 and HDAC, comprising administering toa subject suffering from a condition mediated by both LSD1 and HDAC, atherapeutically effective amount of the compound of Formula I or thepharmaceutical composition.

In an embodiment, the invention relates to a method for the treatmentand/or prevention of a proliferative disorder or cancer, comprisingadministering to a subject suffering from the proliferative disorder orcancer a therapeutically effective amount of the compound of Formula Ior the pharmaceutical composition. In another embodiment, the inventionrelates to the method as described herein, wherein said compound orcomposition is administered in combination with at least one compoundselected from cytotoxic agents and non-cytotoxic agents to a subject inneed thereof.

In yet another embodiment, the invention relates to use of the compoundsof Formula I or the pharmaceutical composition for treatment of acondition mediated by LSD1; treatment and/or prevention of aproliferative disorder or cancer; or treatment of cancer together withother clinically relevant cytotoxic agents or non-cytotoxic agents.

In an embodiment, the invention relates to a method for the treatmentand/or prevention of a condition mediated by LSD1 or a proliferativedisorder or cancer, comprising administering to a subject suffering fromthe condition mediated by LSD1 or the proliferative disorder or cancer,a therapeutically effective amount of the compound or the pharmaceuticalcomposition.

In another embodiment, the invention relates to use of the compounds ofFormula I or the pharmaceutical composition for: treatment of acondition mediated by HDAC; treatment and/or prevention of aproliferative disorder or cancer; or treatment of cancer together withother clinically relevant cytotoxic agents or non-cytotoxic agents.

In yet another embodiment, the invention relates to a method for thetreatment and/or prevention of a condition mediated by HDAC or aproliferative disorder or cancer, comprising administering to a subjectsuffering from the condition mediated by HDAC or the proliferativedisorder or cancer, a therapeutically effective amount of the compoundof Formula I or the pharmaceutical composition.

In an embodiment, the invention relates to use of the compounds ofFormula I or the pharmaceutical composition for: treatment of acondition mediated by both LSD1 and HDAC; treatment and/or prevention ofa proliferative disorder or cancer; or treatment of cancer together withother clinically relevant cytotoxic agents or non-cytotoxic agents.

In another embodiment, the invention relates to a method for thetreatment and/or prevention of a condition mediated by both LSD1 andHDAC or a proliferative disorder or cancer, comprising administering toa subject suffering from the condition mediated by both LSD1 and HDAC orthe proliferative disorder or cancer, a therapeutically effective amountof the compound of Formula I or the pharmaceutical composition.

In yet another embodiment, the invention relates to a method for thetreatment of cancer, said method comprising administering a combinationof the compounds of Formula I or the pharmaceutical composition, withother clinically relevant cytotoxic agents or non-cytotoxic agents to asubject in need thereof.

In an embodiment, the invention relates to a method of treatment ofcancer, said method comprising administering a combination of thecompounds of Formula I or the pharmaceutical composition, with otherclinically relevant immune modulators agents to a subject in need ofthereof.

The invention also provides a method of treatment of cancer in patientsincluding administration of a therapeutically effective amount of acompound of Formula (I).

The invention also provides a method for treatment of proliferativeconditions or cancer, comprising administering to a subject sufferingfrom proliferative conditions or cancer, a therapeutically effectiveamount of a compound of Formula (I), in the presence or absence of otherclinically relevant cytotoxic agents or non-cytotoxic agents to asubject in need thereof.

The present invention provides a method of treatment of a disordercaused by, associated with or accompanied by disruptions of cellproliferation and/or angiogenesis and the subsequent metastasisincluding administration of a therapeutically effective amount of acompound of Formula (I).

The invention provides a method of treatment of cancer in patientincluding administration of effective amount of compounds of Formula(I). The cancer can be either a hematologic malignancy or solid tumor.Hematological malignancy is selected from the group consisting of B-celllymphoma, T-cell lymphoma and leukemia. In the case of solid tumors, thetumors are selected from the group consisting of breast cancer, lungcancer, ovarian cancer, prostate cancer, head cancer, neck cancer, renalcancer, gastric cancer, colon cancer, pancreatic cancer and braincancer.

As discussed above, the compounds of the present invention are usefulfor treating proliferative diseases. A proliferative disease includes,for example, a tumor disease and/or metastases. Compounds of the presentinvention are useful for treating a proliferative disease that isrefractory to the treatment with other chemotherapeutics; or a tumorthat is refractory to treatment with other therapeutics due to multidrugresistance.

Compounds of the present invention are able to slow tumor growth, stoptumor growth or bring about the regression of tumors and to prevent theformation of tumor metastasis (including micrometastasis) and the growthof metastasis (including micrometastasis). In addition, they can be usedin epidermal hyperproliferation.

The compound of formula I of the present invention can be used as aprophylactic or therapeutic agent for cancer. Examples of the cancerinclude, but not restricted to, breast cancer, prostate cancer,pancreatic cancer, gastric cancer, lung cancer, colon cancer, rectalcancer, esophagus cancer, duodenal cancer, tongue cancer, pharyngealcancer, brain tumor, neurinoma, non-small cell lung cancer, small celllung cancer, liver cancer, kidney cancer, bile duct cancer, uterine bodycancer, cervical cancer, ovarian cancer, urinary bladder, skin cancer,hemangioma, malignant lymphoma, malignant melanoma, thyroid cancer, bonetumor, vascular fibroma, retinoblastoma, penile cancer, pediatric solidcancer, lymphoma, myeloma and leukemia (including, for example acutemyelogenous leukemia (AML), chronic myelogenous leukemia (CML), chronicneutrophilic leukemia, chronic eosinophilic leukemia, chroniclymphocytic leukemia (CLL), acute lymphoblastic leukemia (ALL) or hariycell leukemia) or cutaneous T-cell lymphoma (CTCL).

In one embodiment, the invention provides a method of inhibiting bothLSD-1 and HDAC activity comprising administering, to a patient in needof treatment, an amount of a composition comprising a compound offormula I and a pharmaceutically acceptable carrier sufficient toinhibit both LSD-1 and HDAC activity.

In one aspect of this embodiment, the invention provides a compound offormula I for use in inhibiting both LSD-land HDAC. In a related aspect,the invention provides for the use of a compound of formula I for themanufacture of a medicament for inhibiting both LSD-1 and HDAC.

In one embodiment, the invention provides a method of treating and/orpreventing a neurodegenerative disease or disorder comprisingadministering, to a patient in need of treatment, a therapeuticallyeffectively amount of a composition comprising a compound of formula Iand a pharmaceutically acceptable carrier.

In one aspect of this embodiment, the invention provides a compound offormula I for use in treating and/or preventing a neurodegenerativedisorder or condition. In a related aspect, the invention provides forthe use of a compound of formula I for the manufacture of a medicamentfor treating and/or preventing a neurodegenerative disorder orcondition.

In another aspect, the compound may be administered in combinationtherapy by combining the compound of Formula (I) with one or moreseparate agents, not limited to targets such as DNA methyltransferase,heat shock proteins (e.g. HSP90), kinase, epigenetic and other matrixmetalloproteinases.

“Combination therapy” includes the administration of the subjectcompounds in further combination with other biologically activeingredients (such as, but are not limited to, different antineoplasticagent) and non-drug therapies (such as, but are not limited to, surgeryor radiation treatment). The compounds described herein can be used incombination with other pharmaceutically active compounds, preferably,which will enhance the effect of the compounds of the invention. Thecompounds can be administered simultaneously or sequentially to theother drug therapy.

In another aspect, the subject compounds may be combined with theantineoplastic agents (e.g. small molecules, cytotoxic reagents,non-cytotoxic reagents, monoclonal antibodies, antisense RNA and fusionproteins) that inhibit one or more biological targets. Such combinationmay enhance therapeutic efficacy over the efficacy achieved by any ofthe agents alone and may prevent or delay the appearance of resistantvariants.

In another aspect, the subject compounds may be combined withimmunoncology drugs not restricting to PDL-1, IDO, TDO, CTLA4 or anyother drugs which is involved in the immune modulation.

EXAMPLES

The following examples provide the details about the synthesis,activities, and applications of the compounds of the present disclosure.It should be understood the following is representative only, and thatthe invention is not limited by the details set forth in these examples.

There is also provided a process as shown in the following scheme-1, forthe preparation of compounds of the Formula (I), wherein all the groupsare as defined earlier.

The said process for the preparation of the compounds of Formula (I)comprises of the following:Step 1: Compound 1 were reacted with an aldehyde or ketone in proticsolvents such as MeOH, etc., to give the intermediate imine which wasreacted with sodium borohydride (NaBH₄) or its equivalent to give thecompound 2 or compound of 1 were alkylated with the correspondingsubstituted halo compound in the presence of inorganic or organic baseto give the compound 2.Step 2: Hydrolyzing the intermediate compound 2 with an inorganic basegave the corresponding acid. Coupling the acid with activating agentssuch as EDCI.HCl (1 (3-dimethylaminopropyl)-3-ethylcarbodiimidehydrochloride) and HOBt (1-hydroxybenzotriazole) or (1-propylphosphonicanhydride)T₃P/triethylamine and the like in the presence of therespective amine NH₂R₂ to yield the compound of the general Formula (I)or alternatively reacting the intermediate compound 2 with NH₂R₂ and aninorganic base gave the compound of Formula (I)

Synthesis of Intermediates A-1—methyl2-(4-formylpiperidin-1-yl)pyrimidine-5-carboxylate

Step 1: methyl 2-(4-(hydroxymethyl) piperidin-1-yl)pyrimidine-5-carboxylate-II

To a stirred solution of methyl 2-chloropyrimidine-5-carboxylate (I, 2.5g, 14.53 mmol) in DMF (25 mL) was added piperidin-4-ylmethanol (2 g,17.44 mmol) and potassium carbonate (4.01 g, 29.07 mmol) and stirred for5 hours at room temperature. Progress of reaction followed TLC, aftercompletion of reaction, the reaction mixture was concentrated andquenched with water (100 mL) extracted with ethyl acetate (2×150 mL).The organic portion was washed with water, brine, dried over sodiumsulphate and concentrated under reduced pressure to afford the crudeproduct which was purified by column chromatography usingmethanol-dichloromethane gradient to afford the titled product asoff-white solid (II, 3.6 g, 83%). LC-MS m/z calcd for C₁₂H₁₇N₃O₃, 251.1.found 252.1[M+H]⁺.

Step 2: methyl 2-(4-formylpiperidin-1-yl) pyrimidine-5-carboxylate-A-1

To a stirred solution of DMSO (5.6 g, 171.71 mmol) in dichloromethane(40 mL) was added oxalyl chloride (6.02 g, 47.81 mmol) at −78° C.(drop-wise) and continue stirred for 30° C., methyl2-(4-(hydroxymethyl)piperidin-1-yl)pyrimidine-5-carboxylate (II, 3 g,11.95 mmol) dissolved in dichloromethane (10 mL) was slowly added andcontinue stirred for 3 h at −78° C. (drop-wise). To the reaction mixturetriethylamine (14.4 g, 143.42 mmol) was added and stirred for 12 h atroom temperature. Progress of reaction followed by TLC, reaction mixturequenched with ammonium chloride (100 mL), extracted with ethylacetate(2×150 mL). The organic portion was washed with water and brine driedover sodium sulphate and concentrated under reduced pressure to affordthe crude product which was purified by column chromatography usingmethanol-dichloromethane gradient to afford the titled product asoff-white solid (A-1, 2 g, 67%). LC-MS m/z calcd for C₁₂H₁₅N₃O₃, 249.1.found 250.1[M+H]⁺.

A-2 methyl (E)-3-(4-(4-formylpiperidin-1-yl)phenyl)acrylate

The intermediate A-2 was synthesized using methyl-4-fluorocinnamic acidester and piperidin-4-yl-methanol using the procedure for synthesizingA-1. LC-MS m/z calcd for C₁₆H₁₉NO₃ 273.1. found 274.1[M+H]⁺.

A-3—ethyl 2-(4-oxopiperidin-1-yl)pyrimidine-5-carboxylate

The intermediate A-3 was synthesized using ethyl2-chloropyrimidine-5-carboxylate and 4-oxo-piperidine using theprocedure for synthesizing A-1.

LC/MS m/z calcd for C₁₂H₁₅N₃O₃, 249.1. found 250.1 [M+H]⁺.

A-4 methyl2-(2-formyl-5,6-dihydroimidazo[1,2-a]pyrazin-7(8H)-yl)pyrimidine-5-carboxylate

Step 1:2-Hydroxymethyl-5,6-dihydro-8H-imidazo[1,2-a]pyrazine-7-carboxylic acidtert-butyl ester (IV)

To a stirred solution of 7-tert-butyl 2-methyl5,6-dihydroimidazo[1,2-a]pyrazine-2,7(8H)-dicarboxylate (III, 0.42 g,1.42 mmol) in dry tetrahydrofuran (12 mL) was added diisobutylaluminiumhydride (DIBAL-H) (4.97 mL, 4.98 mmol, 1M solution of THF) drop-wise at−35° C. to −40° C. After completion of addition, the reaction mixturewas allowed to stir at room temperature for 3 h. The progress of thereaction was monitored by TLC. The reaction mixture was quenched withsaturated ammonium chloride solution at −30° C. and was extracted withdichloromethane (3×50 mL). The combined organic extract was washed withwater, brine dried over sodium sulphate and concentrated under reducedpressure to get the titled product as an off-white solid (IV, 0.34 g,94%). LC-MS m/z calcd for C₁₂H₁₉N₃O₃, 253.1; found 254.4 [M+H]⁺.

Step 2: (5,6,7,8-Tetrahydro-imidazo[1,2-a]pyrazin-2-yl)-methanolhydrochloride (V)

To a solution of2-hydroxymethyl-5,6-dihydro-8H-imidazo[1,2-a]pyrazine-7-carboxylic acidtert-butyl ester (IV, 0.34 g, 1.34 mmol) in dry methanol (12 mL) wasadded 20% HCl in dioxane (18 mL) at 0° C. and the resulting mixture wasstirred at room temperature for 16 h. The solvent was evaporated underreduced pressure to get the crude product which was triturated withdiethylether to afford the titled product as a pale-yellow solid (V,0.25 g, 95%). LC-MS m/z calcd for C₇H₁₁N₃O, 153.1; found 154.2 [M+H]⁺.

Step 3:2-(2-Hydroxymethyl-5,6-dihydro-8H-imidazo[1,2-a]pyrazin-7-yl)-pyrimidine-5-carboxylicacid methyl ester (VI)

To a suspension of(5,6,7,8-tetrahydro-imidazo[1,2-a]pyrazin-2-yl)-methanol hydrochloride(V, 0.35 g, 1.85 mmol) was added potassium carbonate (0.51 g, 3.71 mmol)at 0° C. and stirred at that temperature for 5 min. Then,2-chloro-pyrimidine-5-carboxylic acid methyl ester (0.38 g, 2.22 mmol)was added and the resulting mixture was stirred at room temperature for15 h. The reaction mixture was quenched with ice and the solvent wasevaporated to get the residue. Water was added and precipitate formedwas filtered, washed with water and n-hexane to afford the pure productas an off-white solid (VI, 0.36 g, 68%). LC-MS m/z calcd for C₁₃H₁₅N₅O₃,289.1; found 290.1 [M+H]⁺.

Step 4:2-(2-Formyl-5,6-dihydro-8H-imidazo[1,2-a]pyrazin-7-yl)-pyrimidine-5-carboxylicacid methyl ester-Intermediate A-4

To a solution of2-(2-Hydroxymethyl-5,6-dihydro-8H-imidazo[1,2-a]pyrazin-7-yl)-pyrimidine-5-carboxylicacid methyl ester (VI, 0.36 g, 1.24 mmol) in dry dichloromethane (15 mL)was added Dess-martin periodinane (1.32 g, 3.11 mmol) at 0° C. and theresulting mixture was stirred at room temperature for 2 h. The progressof the reaction was monitored by TLC. The reaction mixture was quenchedwith saturated sodium bicarbonate solution. Aqueous solution of sodiumthiosulphate (10 mL, 10%) was added and stirred for 15 min. Then dilutedwith dichloromethane and the organic portion was washed with saturatedsodium bicarbonate solution, water and brine solution, dried over sodiumsulphate and concentrated under reduced pressure to afford the crudewhich was then triturated with n-pentane to afford the titled product asan off white solid (A-4, 0.35 g, 95%), LC-MS m/z calcd for C₁₃H₁₃N₅O₃,287.1; found 288.1 [M+H]⁺.

A-5-methyl 7-(4-formylbenzamido)heptanoate-procedure

To a stirred solution of 4-formylbenzoic acid (1 g, 6.66 mmol) andmethyl 7-aminoheptanoate (VII, 1.16 g, 7.33 mmol) in dichloromethane (30mL) was added triethylamine (2.3 mL, 16.6 mmol), the reaction mixturewas stirred at room temperature for 10 min and then cooled reactionmixture to 0° C. and added T₃P (6.35 mL, 10 mmol) and was stirred atroom temperature for 3 h. Reaction was monitored by TLC. Aftercompletion of reaction, the mixture was quenched with ice. The reactionmixture was diluted with water and extracted with dichloromethane (3×25mL). The organic portion was washed with water, brine, dried over sodiumsulphate and concentrated under reduced pressure to get the titlecompound as solid. (A-5, 1.8 g, 92%). LC-MS m/z calcd for C₁₆H₂₁NO₄,291.1; found 292.2 [M+H]⁺.

A-6-1-(2,2,2-trifluoroacetyl)piperidine-4-carbaldehyde

Step 1: 2,2,2-trifluoro-1-(4-(hydroxymethyl)piperidin-1-yl)ethanone (IX)

To a stirred solution of piperidin-4-ylmethanol (VIII, 5.0 g, 4.3 mmol)in dichloromethane (200 mL) was added triethylamine at 0° C. andfollowed by trifluoro acetic anhydride, and the reaction mixture wasstirred at room temperature about 12 h. The progress of the reaction wasmonitored by TLC. The reaction mixture was diluted with dichloromethane,the organic portion was washed with saturated ammonium chloride, water,followed by brine solution, dried over sodium sulphate and concentratedunder reduced pressure to get the product as sticky oil (IX, 8.5 g,92%). LC-MS m/z calcd for C₈H₁₂F₃NO, 211.1; found 212.1 [M+H]⁺.

Step 2: 1-(2,2,2-trifluoroacetyl)piperidine-4-carbaldehyde (A-6)

A solution of dimethyl sulfoxide (4 mL) and dichloromethane (60 mL) wascooled to −68° C. Oxalyl chloride (3.2 mL) was slowly added drop-wiseand the reaction mixture was stirred for 30 min at −68° C. Then asolution of 2,2,2-trifluoro-1-(4-(hydroxymethyl)piperidin-1-yl)ethanone(IX, 2 g, 9.48 mmol) in 4 mL of dichloromethane and was added dropwiseat −68° C., after completion of addition, the reaction mixture wasstirred for 1.5 h at −68° C. and this was followed by drop-wise additionof triethylamine at −68° C. The reaction mixture was stirred at −68° C.for 4-6 h. The reaction mixture was then allowed to warm to roomtemperature and the stirring was continued for 16 h. The progress of thereaction was monitored by TLC. The reaction mixture was diluted withethylacetate and the organic portion was washed with water, saturatedammonium chloride, brine, dried over sodium sulphate and concentratedunder reduced pressure to get the product as sticky oil (A-6, 1.9 g,96%), LC-MS m/z calcd for C₈H₁₀F₃NO₂, 209.1; found 210.1 [M+H]⁺.

A-7: Ethyl 4-((4-formyl-1H-1,2,3-triazol-1-yl)methyl)benzoate

Step-1: Ethyl4-((4-(hydroxymethyl)-1H-1,2,3-triazol-1-yl)methyl)benzoate-XI

To a stirred solution of ethyl 4-(azidomethyl)benzoate (X, 2 g, 9.75mmol) in DMF (80 mL) was added propargyl alcohol (0.6 mL, 10.7 mmol) andDIPEA (2.7 mL, 14.6 mmol) and then copper (I) iodide (0.9 g, 4.87 mmol)was added. The reaction mixture was stirred for 30 min at roomtemperature. Saturated ammonium chloride solution with few drop ofammonia (20 mL) was added and extracted with ethylacetate (2×100 mL).The organic portion was washed with water, brine, dried over sodiumsulphate and concentrated under reduced pressure to afford the crudecompound which was purified by column chromatography usingethylacetate-hexane gradient as eluent to afford the titled product assticky oil (XI, 2.1 g, 87%). LC-MS m/z calcd for C₁₃H₁₅N₃O₃, 261.1;found 262.1 [M+H]⁺.

Step-2: ethyl4-((4-formyl-1H-1,2,3-triazol-1-yl)methyl)benzoate-Intermediate A-7

To a stirred solution of ethyl4-((4-(hydroxymethyl)-1H-1,2,3-triazol-1-yl)methyl)benzoate (XI, 1 g,3.83 mmol) in ethylacetate (25 mL) was added IBX (1.6 g, 5.74 mmol) andheated at 75° C. for 16 h. Water (50 mL) was added and extracted withethyl acetate (2×50 mL). The organic portion was washed with water,brine, dried over sodium sulphate and concentrated under reducedpressure to afford the crude compound which was purified by columnchromatography using ethylacetate-hexane gradient as eluent to affordthe titled product as solid (A-7, 0.75 g, 76%). LC-MS m/z calcd forC₁₃H₁₃N₃O₃, 259.1; found 260.1 [M+H]⁺.

A-8 and A-9: ethyl 4-(3-(4-formyl-1H-imidazol-1-yl)propyl)benzoate andethyl 4-(3-(5-formyl-1H-imidazol-1-yl)propyl)benzoate

To a stirred solution of sodium hydride (0.124 g, 5.20 mmol) in THF (3.5mL) was added 1H-imidazole-4-carbaldehyde (0.5 g, 5.20 mmol) portionwise at 0° C. After 1 h stirring, ethyl 4-(3-bromopropyl)benzoate (XII,1.4 g, 5.20 mmol) and was 18-crown ether (0.2 g) was added at 0° C. andthe temperature was allowed to warm to room temperature. The reactionmixture was then heated at 60° C. for 18 h. The reaction mixture wasquenched with ice-water and extracted with ethylacetate (2×50 mL). Theorganic portion was washed with water, brine, dried over sodium sulphateand concentrated under reduced pressure to afford the crude compoundwhich was purified by column chromatography using ethylacetate-hexanegradient as eluent to afford the titled product as sticky oil (A-8, 0.19g, 13%), ¹HNMR (400 MHz, DMSO-d₆): δ 9.68 (s, 1H), 8.09 (s, 1H),7.88-7.84 (m, 3H), 7.33 (d, 2H, J=8 Hz), 4.28 (q, 2H, J=6.8 Hz), 4.06(t, 2H, J=6.8 Hz), 2.62 (t, 2H, J=7.2 Hz), 2.13-2.06 (m, 2H), 1.29 (t,3H, J=7.2 Hz). LC-MS m/z calcd for C₁₆H₁₈N₂O₃, 286.1; found 287.1 [M+H]⁺and stick oil (A-9, 0.2 g, 15%), ¹HNMR (400 MHz, DMSO-d₆): δ 9.70 (s,1H), 8.06 (s, 1H), 7.88 (s, 1H), 7.85 (d, 2H, J=8 Hz), 7.31 (d, 2H,J=7.6 Hz), 4.32-4.25 (m, 4H), 2.62 (t, 2H, J=8 Hz), 2.04-1.95 (m, 2H),1.29 (t, 3H, J=7.2 Hz). LC-MS m/z calcd for C₁₆H₁₈N₂O₃, 286.1; found287.1 [M+H]⁺.

A-10: ethyl 4-((4-formyl-1H-imidazol-1-yl)methyl)benzoate

Intermediate A-10 was synthesized starting from ethyl4-(bromomethyl)benzoate and 1H-imidazole-4-carbaldehyde followingprotocol given for A-8. LC-MS m/z calcd for C₁₄H₁₄N₂O₃, 258.1. found259.1 [M+H]⁺.

A-11: ethyl 4-(3-(4-formyl-1H-pyrazol-1-yl)propyl)benzoate

Intermediate A-11 was synthesized starting from1H-pyrazole-4-carbaldehyde and methyl 4-(3-bromopropyl)benzoatepyrazolefollowing protocol given for A-8. LC-MS m/z calcd for C₁₆H₁₈N₂O₃, 286.1;found 287.0 [M+H]⁺.

A-12-methyl 4-((4-formyl-1H-pyrazol-1-yl)methyl)benzoate

Intermediate A-12 was synthesized starting from1H-pyrazole-4-carbaldehyde and ethyl 4-(bromomethyl)benzoate followingprotocol given for A-8. LC-MS m/z calcd for C₁₄H₁₄N₂O₃, 258.1; found259.1 [M+H]⁺.

A-13-methyl 4-(2-(4-formyl-1H-imidazol-1-yl)ethyl)benzoate

Intermediate A-13 was synthesized starting from1H-pyrazole-4-carbaldehyde and methyl 4-(bromoethyl)benzoate followingprotocol given for A-8. LC-MS m/z calcd for C₁₄H₁₄N₂O₃, 258.1; found259.1 [M+H]⁺.

A-14: Methyl4-((2-formyl-5,6-dihydroimidazo[1,2-a]pyrazin-7(8H)-yl)methyl)benzoate

Step 1: Methyl4-((2-(hydroxymethyl)-5,6-dihydroimidazo[1,2-a]pyrazin-7(8H)-yl)methyl)benzoate(XIII)

To a suspension of(5,6,7,8-Tetrahydro-imidazo[1,2-a]pyrazin-2-yl)-methanol hydrochloride(V, 0.52 g, 2.75 mmol) was added potassium carbonate (1.14 g, 8.27 mmol)at 0° C. and stirred at that temperature for 5 min. Then methyl4-(bromomethyl)benzoate (0.69 g, 3.03 mmol) was added and the resultingmixture was stirred at room temperature for 3 h. Reaction was monitoredby TLC, after completion of the reaction, the reaction mixture wasquenched with ice and extracted with dichloromethane. The organic layerwas washed with cold water, brine, dried over sodium sulphate andconcentrated under reduced pressure to afford the required product(XIII, 0.47 g, 52%). LC-MS m/z calcd for C₁₆H₁₉N₃O₃, 301.1; found 302.2[M+H]⁺.

Step 2: Methyl4-((2-formyl-5,6-dihydroimidazo[1,2-a]pyrazin-7(8H)-yl)methyl)benzoate-IntermediateA-14

To a solution of methyl4(2-hydroxymethyl)-5,6-dihydroimidazo[1,2-a]pyrazin-7(8H)yl)methyl)benzoate(XIII, 0.43 g, 1.42 mmol) in dry dichloromethane (15 mL) was addedDess-martin periodinane (1.51 g, 3.57 mmol) at 0° C. and the resultingmixture was stirred at room temperature for 2 h. The progress of thereaction was monitored by TLC. The reaction mixture was quenched withsaturated sodium bicarbonate solution. A 10% aqueous solution of sodiumthiosulphate (5 mL) was added and stirred for 15 min. Then diluted withdichloromethane and the organic portion was washed with saturated sodiumbicarbonate solution, water and brine solution dried over sodiumsulphate and concentrated under reduced pressure to afford the crudewhich was then triturated with n-pentane to afford the titled product asan off white solid (A-14, 0.41 g, 96%). LC-MS m/z calcd for C₁₆H₁₇N₃O₃,299.1; found 300.1 [M+H]⁺.

A-15-methyl 4-(2-(4-formylpiperidin-1-yl)ethyl)benzoate

Intermediate A-15 was synthesized starting from piperidin-4-yl-methanoland methyl 4-(bromoethyl)benzoate following protocol given for A-14.LC-MS m/z calcd for C₁₆H₂₁NO₃, 275.1; found 276.1 [M+H]⁺.

A-16-methyl 4-(3-(4-oxopiperidin-1-yl)propyl)benzoate

Intermediate A-16 was synthesized starting from 4-oxo-piperidinehydrochloride salt and methyl 4-(bromopropyl)benzoate following protocolgiven for A-14. LC-MS m/z calcd for C₁₆H₂₁NO₃, 275.1; found 276.1[M+H]⁺.

A-17—ethyl 4-(3-(4-formyl-2-oxopiperidin-1-yl)propyl)benzoate

Intermediate A-17 was synthesized starting from2-oxo-piperidin-yl-4-methanol and methyl 4-(bromopropyl)benzoatefollowing protocol given for A-14. LC-MS m/z calcd for C₁₈H₂₃NO₄, 317.1;found 318.0 [M+H]⁺.

A-18-methyl4-(3-(2-formyl-5,6-dihydroimidazo[1,2-a]pyrazin-7(8H)-yl)propyl)benzoate

Step 1:4-[3-(2-Hydroxymethyl-5,6-dihydro-8H-imidazo[1,2-a]pyrazin-7-yl)-propyl]-benzoicacid ethyl ester (XIV)

To a stirred solution of(5,6,7,8-tetrahydro-imidazo[1,2-a]pyrazin-2-yl)-methanol. HCl salt (V,0.1 g, 0.53 mmol) in methanol (8 mL) was added 4-(3-oxo-propyl)-benzoicacid ethylester (0.13 g, 0.63 mmol) and sodium bicarbonate (0.044 g,0.53 mmol) and molecular sieves (approx 1 g) at room temperature and theresulting mixture was heated to reflux for 30 min. Cooled to roomtemperature and sodium cyanoborohydride (0.036 g, 0.58 mmol) was addedand stirred at room temperature for 15 h. Ice was added and the reactionmixture was filtered. The solvent was evaporated to get the residue.Water was added and extracted with dichloromethane (2×30 mL). Theorganic portion was washed with water and brine, dried over sodiumsulphate and concentrated under reduced pressure to afford the crudecompound which was purified by column chromatography to afford thetitled product as a colourless oil. (XIV, 0.09 g, 50%). LC-MS m/z calcdfor C₁₉H₂₅N₃O₃, 343.2; found 344.3 [M+H]⁺.

Step 2:4-[3-(2-Formyl-5,6-dihydro-8H-imidazo[1,2-a]pyrazin-7-yl)-propyl]-benzoicacid ethyl ester-Intermediate A-18

To a stirred solution of4-[3-(2-hydroxymethyl-5,6-dihydro-8H-imidazo[1,2-a]pyrazin-7-yl)-propyl]-benzoicacid ethyl ester (XIV, 0.09 g, 0.26 mmol) in dry dichloromethane (10 mL)was added Dess-martin periodinane (0.28 g, 0.65 mmol) at 0° C. and theresulting mixture was stirred at room temperature for 3 h. The progressof the reaction was monitored by TLC. The reaction mixture was quenchedwith saturated sodium bicarbonate solution. A 10% aqueous solution ofsodium thiosulphate (1 mL) was added and stirred for 15 min, thendiluted with dichloromethane (20 mL) and the organic portion was washedwith saturated sodium bicarbonate solution, water and brine solutiondried over sodium sulphate and concentrated under reduced pressure toafford the required product as yellow solid (A-18, 0.08 g, 90%) whichwas carried to next step without further purification. LC-MS m/z calcdfor C₁₉H₂₃N₃O₃, 341.1; found 342.2 [M+H]⁺.

A-19-methyl 4-(2-(4-formylpiperidin-1-yl)propyl)benzoate

Intermediate A-19 was synthesized starting from piperidin-4-yl-methanoland 4-(3-Oxo-propyl)-benzoic acid ethylester following protocol givenfor A-18. LC-MS m/z calcd for C₁₈H₂₅NO₃, 303.2; found 304.1 [M+H]⁺.

A-20-methyl4-(3-(7-formyl-3,4-dihydroisoquinolin-2(1H)-yl)propyl)benzoate

Intermediate A-20 was synthesized starting from(1,2,3,4-tetrahydroisoquinolin-6-yl)methanol hydrochloride and4-(3-oxo-propyl)-benzoic acid ethylester following protocol given forA-18. LC-MS m/z calcd for C₂₁H₂₃NO₃, 337.2; found 338.1 [M+H]⁺.

A-21—ethyl4-(3-(6-formyl-3,4-dihydroisoquinolin-2(1H)-yl)propyl)benzoate

Intermediate A-21 was synthesized starting from(1,2,3,4-tetrahydroisoquinolin-7-yl)methanol hydrochloride and4-(3-oxo-propyl)-benzoic acid ethylester following protocol given forA-18. LC-MS m/z calcd for C₂₂H₂₅NO₃, 351.2; found 352.2 [M+H]⁺.

A-22-methyl 4-((7-formyl-3,4-dihydroisoquinolin-2(1H)-yl)methyl)benzoate

Intermediate A-22 was synthesized starting from(1,2,3,4-tetrahydroisoquinolin-7-yl)methanol hydrochloride and4-formyl-1-benzoic acid methylester following protocol given for A-18.LC-MS m/z calcd for C₁₉H₁₉NO₃, 309.1; found 310.1 [M+H]⁺.

A-23: Methyl 4-(3-oxo-3-(4-oxopiperidin-1-yl)propyl)benzoate

To a stirred solution of 3-(4-(methoxycarbonyl)phenyl)propanoic acid(0.6 g, 2.88 mmol) and piperidine-4-onehydrochloride (0.57 g, 5.76mmol), in dichloromethane (15 mL) was added triethylamine (1.2 g, 8.64mmol), the reaction was stirred at room temperature for 10 min, thencooled reaction mixture to 0° C. and added T₃P (2.14 mL, 7.20 mmol), andthe resulting mixture was stirred at room temperature for 3 h. Reactionwas monitored by TLC, after completion of reaction and the mixture wasquenched with ice. The reaction mixture was diluted with water andextracted with dichloromethane (3×25 mL). The organic portion was washedwith water, brine, dried over sodium sulphate and concentrated underreduced pressure to get the required product as pale-yellow oil. (A-23,0.79 g, 94%). LC-MS m/z calcd for C₁₆H₁₉NO₄, 289.1; found 290.2 [M+H]⁺.

A-24-methyl 4-(2-(4-formylpiperidin-1-yl)-2-oxoethyl)benzoate-procedure

Step 1: methyl4-(2-(4-(hydroxymethyl)piperidin-1-yl)-2-oxoethyl)benzoate-XVI

To a stirred solution of 2-(4-(methoxycarbonyl)phenyl)acetic acid (1 g,5.15 mmol) and piperidin-4-ylmethanol (0.65 g, 5.67 mmol), indichloromethane (25 mL) was added triethylamine (1.07 mL, 7.72 mmol),the reaction was stirred at room temperature for 10 min, then cooledreaction mixture to 0° C. and added T₃P (4.91 mL, 7.72 mmol), and theresulting mixture was stirred at room temperature for 3 h. Reaction wasmonitored by TLC, after completion of reaction, the mixture was quenchedwith ice. The reaction mixture was diluted with water and extracted withdichloromethane (3×25 mL). The organic portion was washed with water,brine, dried over sodium sulphate and concentrated under reducedpressure to get the title product as gummy solid. (XVI, 1.2 g, 80%).LC-MS m/z calcd for C₁₆H₂₁NO₄, 291.1; found 292.1 [M+H]⁺.

Step 2:methyl 4-(2-(4-formylpiperidin-1-yl)-2-oxoethyl)benzoate-A-24

To a stirred solution of oxalyl chloride (0.23 mL, 2.69 mmol) in drydichloromethane (5 mL) was added dried dimethylsulfoxide (0.28 mL, 4.06mmol) dropwise at −78° C. and stirred for 15 min. A solution of methyl4-(2-(4-(hydroxymethyl)piperidin-1-yl)-2-oxoethyl)benzoate (XVI, 0.2 g,0.68 mmol) in dry dichloromethane was added drop-wise followed by theslow addition of triethylamine (6.25 mL, 45.36 mmol) at −78° C. Theresulting mixture was stirred at −78° C. for 2 h. The reaction mixturewas diluted with dichloromethane (100 mL). The organic portion waswashed with water, brine, dried over sodium sulphate and concentratedunder reduced pressure to afford the titled product as light yellowcolour oil (A-24, 0.2 g, quantitative yield). LC-MS m/z calcd forC₁₆H₁₉NO₄, 289.1; found 290.1 [M+H]⁺.

A-25—ethyl5-(4-oxobutanoyl)-4,5,6,7-tetrahydrothieno[3,2-c]pyridine-2-carboxylate

Step-1 ethyl5-(4-hydroxybutanoyl)-4,5,6,7-tetrahydrothieno[3,2-c]pyridine-2-carboxylate-XVIII

To a solution of ethyl4,5,6,7-tetrahydrothieno[3,2-c]pyridine-2-carboxylate TFA salt (XVII,0.5 g, 1.50 mmol) in triethylamine (1 mL) was addeddihydrofuran-2(3H)-one (0.11 mL, 1.50 mmol) and heated at 100° C. for 16h. The reaction mixture was diluted with dichloromethane (50 mL) andwashed with 1N HCl solution, water, brine solution, dried over sodiumsulphate and concentrated under vacuum to get crude product which waspurified by column chromatography using methanol-dichloromethanegradient to afford the titled product as sticky oil (XVIII, 0.2 g, 44%).LC-MS m/z calcd for C₁₄H₁₉NO₄S, 297.1; found 298.2 [M+H]⁺.

Step-2: ethyl5-(4-oxobutanoyl)-4,5,6,7-tetrahydrothieno[3,2-c]pyridine-2-carboxylate-A-25

To a stirred solution of oxalyl chloride (0.23 mL, 2.69 mmol) in drydichloromethane (5 mL) was added dry dimethylsulfoxide (0.28 mL, 4.06mmol) drop-wise at −78° C. and stirred for 15 min. A solution of ethyl5-(4-hydroxybutanoyl)-4,5,6,7-tetrahydrothieno[3,2-c]pyridine-2-carboxylate(XVIII, 0.2 g, 0.67 mmol) in dry dichloromethane was added drop-wisefollowed by the slow addition of triethylamine (6.25 mL, 45.36 mmol) at−78° C. The resulting mixture was stirred at −78° C. for 2 h. Thereaction mixture was diluted with dichloromethane (100 mL). The organicportion was washed with water and brine dried over sodium sulphate andconcentrated under reduced pressure to afford the titled product aslight yellow colour oil (A-25, 0.2 g, quantitative yield). LC-MS m/zcalcd for C₁₄H₁₇NO₄S, 295.1; found 296.2 [M+H]⁺.

A-26—ethyl2-(4-oxobutanoyl)-1,2,3,4-tetrahydroisoquinoline-7-carboxylate

Intermediate A-26 was synthesized starting from ethyl1,2,3,4-tetrahydroisoquinoline-7-carboxylate and dihydrofuran-2(3H)-onefollowing protocol given for A-25. LC-MS m/z calcd for C₁₆H₁₉NO₄, 289.1;found 290.1 [M+H]⁺.

A-27—ethyl 2-(4-oxobutanoyl)isoindoline-5-carboxylate

Intermediate A-27 was synthesized starting from ethylisoindoline-5-carboxylate and dihydrofuran-2(3H)-one following protocolgiven for A-25. LC-MS m/z calcd for C₁₅H₁₇NO₄, 275.1; found 276.1[M+H]⁺.

A-28-ethyl 4-(3-(4-formyl-1H-1,2,3-triazol-1-yl)propyl)benzoate

Intermediate A-28 was synthesized starting from ethyl4-(3-azidopropyl)benzoate following protocol given for A-7. LC-MS m/zcalcd for C₁₅H₁₇N₃O₃, 287.1; found 288.1 [M+H]⁺.

A-29-methyl 4-(3-(4-formylpiperidin-1-yl)-3-oxopropyl)benzoate

Intermediate A-29 was synthesized starting from piperidin-4-ylmethanoland 3-(4-(methoxycarbonyl)phenyl)propanoic acid following the protocolgiven for A-24. LC-MS m/z calcd for C₁₈H₂₃NO₄, 317.1; found 318.2[M+H]⁺.

A-30: ethyl 2-(3-oxopropyl)thiazole-4-carboxylate

Step-1: ethyl-2(-3-hydroxyprop-1-yn-1-yl)thiazole-4-carboxylate-XX

To a ethyl-2-bromothioazole-4-carboxylate (XIX, 4.0 g, 16.0 mmol) in aseal tube was added prop-2-yn-1-ol (1.07 g, 18 mmol), triethylamine(5.92 ml, 42.0 mmol), CuI (0.16 g, 0.8 mmol) and acetonitrile (60 mL)and then degassed with argon for 5 min. PdCl₂(PPh₃)₂ (0.59 g, 8.0 mmol)was added and heated the seal tube at 80° C. for 16 h. After completionof reaction, the reaction mixture was cooled to room temperature andfiltered through celite bed. The filtrate was concentrated under vacuumto afford the crude product which was purified by flash columnchromatography using ethylacetate-hexane gradient to afford titleproduct as brown color liquid (XX, 1.3 g, 36%). LC-MS m/z calcd forC₉H₉NO₃S, 211.0; found 212.0 [M+H]⁺.

Step-2: ethyl 2-(3-hydroxypropyl)thiazole-4-carboxylate-XXI

To a stirred solution of ethyl2(-3-hydroxyprop-1-yn-1-yl)thiazole-4-carboxylate (XX, 1.3 g, 6.1 mmol)in ethanol (20 mL) was added PtO₂ (0.069 mg, 3.0 mmol), triethylamine(0.6 mL, 4.3 mmol) and stirred under hydrogen gas at 30 psi for 3 h.After completion of reaction, the reaction mixture was filtered throughcelite bed. The filtrate was concentrate under vacuum to get the crudeproduct which was purified by flash column chromatography usingethylacetate-hexane gradient to afford the title product as yellow colorliquid (XXI, 0.5 g, 50%). LC-MS m/z calcd for C₉H₁₃NO₃S, 215.1; found216.1 [M+H]⁺.

Step-3:ethyl 2-(3-oxopropyl)thiazole-4-caroboxylate-A30

To a stirred solution of dimethylsulfoxide (0.85 mL, 20.0 mmol) in drydichloromethane (20 mL) was added oxalyl chloride (0.71 mL, 8.3 mmol)drop-wise at −70° C. and stirred at same temperature for 30 min. Thensolution of ethyl 2-(3-hydroxypropyl)thiazole-4-carboxylate (0.45 g, 2.0mmol) in dichloromethane (4 mL) was added drop-wise. After completion ofaddition, the reaction mixture was stirred at −70° C. for additional 2h. Triethylamine (3.3 mL, 24.0 mmol) was slowly added and stirred for 20min. Then the reaction mixture was warmed to room temperature. Aftercompletion of reaction, the reaction was quenched with water, organiclayer was separated. The organic layer was washed with water, brinesolution, dried over sodium sulphate and concentrated to get crude whichwas purified by flash column chromatography using ethylacetate-hexanegradient to afford the title product as yellow liquid (A30, 0.4 g, 90%).LC-MS m/z calcd for C₉H₁₁NO₃S, 213.0; found 214.1 [M+H]⁺.

A-31: ethyl 2-(3-oxopropyl)thiazole-5-carboxylate

The compound was synthesized using ethyl 2-bromothiazole-5-carboxylatefollowing the procedure for synthesis of A-30. LC-MS m/z calcd forC₉H₁₁NO₃S, 213.0; found 214.1 [M+H]⁺.

A-32: methyl 2-(3-oxopropyl)oxazole-4-carboxylate

Step-1: methyl (4-((tert-butyldiphenylsilyl)oxy)butanoyl)serinate-XXIII

To a stirred solution of serine methyl ester (3.68 g, 23.7 mmol) inacetonitrile (60 mL) was added EDC.HCl (4.55 g, 23.7 mmol),triethylamine (3.76 mL, 26.86 mmol) and stirred for 5 min at roomtemperature and then 4-((tert-butyldiphenylsilyl)oxy)butanoic acid(XXII, 0.54 g, 15.8 mmol) was added and stirred for 1 h at argonatmosphere. After completion of reaction, the reaction mixture wasquenched with water (100 mL) and diluted with ethylacetate. The organiclayer was separated and washed with 1N HCl solution, water, brine, driedover sodium sulphate and concentrated to get crude product which waspurified by flash column chromatography using ethylacetate-hexanegradient to afford the title product as colorless liquid (XXIII, 2.46 g,63%). LC-MS m/z calcd for C₂₄H₃₃NO₅Si, 443.2; found 444.2 [M+H]⁺.

Step-2: methyl2-(3-((tert-butyldiphenylsilyl)oxy)propyl)oxazole-4-carboxylate-XXIV

To a stirred solution of methyl(4-((tert-butyldiphenylsilyl)oxy)butanoyl)(hydroxymethyl)carbamate(XXIII, 2.46 g, 5.50 mmol) in dichloromethane (25 mL) was addeddiethylaminosulfur trifluoride (DAST, 0.8 mL, 6.10 mmol) at −78° C. andthen stirred for 2 h. Potassium carbonate (2.27 g, 16.50 mmol) was addedand then stirred at −20° C. for 1 h. After completion of reaction, themixture was quenched with water (50 mL). The organic layer wasseparated, dried over sodium sulphate and concentrated under vacuum. Theresultant crude product was dissolved in dichloromethane (35 mL) andthen followed by addition of 1,8-Diazabicyclo(5.4.0)undec-7-ene (DBU,2.46 mL, 16.5 mmol). The reaction mixture was cooled to 0° C. Thesolution of CBrCl₃ (1.14 mL, 11.5 mmol) in dichloromethane (4 mL) wasadded drop-wise and stirred for 10 h at room temperature. Aftercompletion of reaction, the mixture was diluted with ethylacetate (50mL) and washed with 1N HCl, water, saturated aqueous sodium bicarbonatesolution, brine, dried over sodium sulphate and concentrated undervacuum to get crude product which was purified by flash columnchromatography using ethylacetate-hexane gradient to afford the titleproduct colorless oil (XXIV, 0.86 g, 36%). LC-MS m/z calcd forC₂₄H₂₉NO₄Si, 423.3; found 424.3 [M+H]⁺.

Step-3: methyl 2-(3-hydroxypropyl)oxazole-4-carboxylate-XXV

To a stirred solution of methyl2-(3-((tert-butyldiphenylsilyl)oxy)propyl)oxazole-4-carboxylate (XXIV,0.86 g, 2.0 mmol) in THF (5 mL) was added TBAF (4.1 mL, 4.10 mmol) andstirred for 1 h at room temperature under argon atmosphere. Aftercompletion of reaction, the mixture was quenched with brine solution andextracted with ethylacetate (25 mL×5). The organic layer was dried oversodium sulphate and concentrated under vacuum to get crude product waspurified by flash column chromatography using ethylacetate-hexanegradient to afford the title product brown coloured liquid (XXV, 0.3 g,81%). LC-MS m/z calcd for C₈H₁₁NO₄, 185.1; found 186.1 [M+H]⁺.

Step-4: methyl 2-(3-oxopropyl)oxazole-4-carboxylate-A32

A-32

To a stirred solution of dimethylsulfoxide (0.57 mL, 8.1 mmol) in drydichloromethane (10 mL) was added oxalyl chloride (0.46 mL, 5.0 mmol)drop-wise at −70° C. and stirred at same temperature for 30 min. Thensolution of methyl 2-(3-hydroxypropyl)oxazole-4-carboxylate (0.25 g,1.35 mmol) in dichloromethane (1 mL) was added drop-wise. Aftercompletion of addition, the reaction was stirred at −70° C. foradditional 2 h. Triethylamine (2.2 mL, 24.0 mmol) was slowly added andstirred for 20 min. Then the reaction mixture was warmed to roomtemperature. After completion of reaction, the reaction was quenchedwith water, organic layer was separated. The organic layer was washedwith water, brine solution, dried over sodium sulphate and concentratedto get crude product which was purified by flash column chromatographyusing ethylacetate-hexane gradient to afford the title product as yellowliquid (A32, 0.2 g, 81%). LC-MS m/z calcd for C₈H₉NO₄, 183.1; found184.1 [M+H]⁺.

A-33-methyl(E)-4-(3-(4-formylpiperidin-1-yl)-3-oxoprop-1-en-1-yl)benzoate

Step-1: methyl(E)-4-(3-(4-(hydroxymethyl)piperidin-1-yl)-3-oxoprop-1-en-1-yl)benzoate-XXVII

To a stirred solution of (E)-3-(4-(methoxycarbonyl)phenyl)acrylic acid(XXVI, 3 g, 14.50 mmol) and piperidin-4-yl-methanol (2.2 g, 18.9 mmol)in DMF (50 mL) was added EDC.HCl (2.5 g, 16.0 mmol), HOBt (2.1 g, 16.0mmol) and DIPEA (3.7 mL, 29.0 mmol) at 0° C. and the resulting mixturewas stirred at room temperature for 16 h. The reaction mixture wasconcentrated under vacuum. The resultant crude was diluted withethylacetate and washed with water, brine, dried over sodium sulphateand concentrated under reduced pressure to get the crude product whichwas purified by column chromatography using methanol-dichloromethanegradient to afford the titled product as colorless solid (XXVII, 2.1 g,48%). LC-MS m/z calcd for C₁₇H₂₁NO₄, 303.2; found 304.2 [M+H]⁺.

Step-2: methyl(E)-4-(3-(4-formylpiperidin-1-yl)-3-oxoprop-1-en-1-yl)benzoate-A33

To a stirred solution of dimethylsulfoxide (2.8 mL, 39.6 mmol) in drydichloromethane (40 mL) was added oxalyl chloride (2.2 mL, 26.0 mmol)drop-wise at −70° C. and stirred at same temperature for 30 min. Then asolution of methyl(E)-4-(3-(4-(hydroxymethyl)piperidin-1-yl)-3-oxoprop-1-en-1-yl)benzoate(XXVI, 2 g, 6.60 mmol) in dichloromethane (10 mL) was added drop-wise.After completion of addition, the reaction mixture was stirred at −70°C. for additional 2 h. Triethylamine (11 mL, 79.2 mmol) was slowly addedand stirred for 20 min. Then the reaction mixture was warmed to roomtemperature. After completion of reaction, the reaction was quenchedwith water, organic layer was separated. The organic layer was washedwith water, brine, dried over sodium sulphate and concentrated to affordthe title product A-33 as yellow liquid (2 g, quantitative yield). LC-MSm/z calcd for C₁₇H₁₉NO₄, 301.1; found 302.1 [M+H]⁺.

Synthesis of Intermediates-Amines B-1 andB-2—(1R,2S)-2-(4-fluorophenyl)cyclopropanamine hydrochloride (I-8) and(1S,2R)-2-(4-fluorophenyl)cyclopropanamine hydrochloride (I-9)

Step 1: 2-((1S,2R)-2-(4-fluorophenyl)cyclopropyl)isoindoline-1,3-dioneand 2-((1R,2S)-2-(4-fluorophenyl)cyclopropyl)isoindoline-1,3-dione-XXIX

A mixture of 2-(4-fluoro-phenyl)-cyclopropylamine hydrochloride (XXVIII,1.5 g, 7.99 mmol), isobenzofuran-1,3-dione (1.77 g, 11.99 mmol) anddiisopropylethylamine (4.27 mL, 23.97 mmol) was heated in a sealed tubeat 150° C. for 12 h and cooled to room temperature. The reaction mixturewas diluted with ethylacetate (3×50 mL). The organic portion was washedwith water and brine dried over sodium sulphate and concentrated underreduced pressure to afford the crude compound which was purified bycolumn chromatography to afford the racemic product (1.9 g). The racemicproduct was separated by chiral Prep. HPLC, Chiralpak ia (250 mm×4.6mm×5 μm) using 0.1% TFA in ACN:MeOH (20:80%) solvent to get isomer 1(0.73 g) and isomer 2 (0.77 g). LC-MS m/z calcd for C₁₇H₁₂FNO₂, 281.1;found 282.2 [M+H]⁺.

(1R,2S)-2-(4-fluorophenyl)cyclopropanamine

To a stirred solution of2-[2-(4-fluoro-phenyl)-cyclopropyl]-isoindole-1,3-dione (isomer 2, 0.77g, 2.73 mmol) in dichloromethane and ethanol mixture (12 mL, 5:1) wasadded hydrazine hydrate (0.41 mL, 8.21 mmol) at room temperature and theresulting mixture was stirred at room temperature for 3 h. The progressof the reaction was monitored by TLC. A precipitate formed which wasfiltered and washed with dichloromethane. The filtrate was evaporated togive the product as yellow oil (0.47 g, 95%). The crude was carried tonext step without further purification. LC-MS m/z calcd for C₉H₁₀FN,151.1; found 152.2 [M+H]⁺.

B-2 (Isomer 2): (1R,2S)-2-(4-fluorophenyl)cyclopropanamine hydrochloride

To a stirred solution of 2-(4-fluoro-phenyl)-cyclopropylamine (chirallypure, 0.47 g, 2.108 mmol) in dioxane (5 mL) was added HCl in dioxanesolution (2 mL) at 0° C. and the resulting mixture was stirred at roomtemperature for 2 h. Cooled to room temperature and the solvent wasevaporated to get the residue which was triturated with diethyl ether toafford the product as an off-white solid (B-2, 0.42 g, 72%). LC-MS m/zcalcd for C₉H₁₀FN, 151.1; found 152.2 [M+H]⁺.

B-1 (Isomer 1): (1S,2R)-2-(4-fluorophenyl)cyclopropanamine hydrochloride

The compound was synthesized from2-((1R,2S)-2-(4-fluorophenyl)cyclopropyl)isoindoline-1,3-dione (B-1,isomer 1) by following the same synthesis procedure of(1R,2S)-2-(4-fluorophenyl)cyclopropanamine hydrochloride, LC-MS m/zcalcd for C₉H₁₀FN, 151.1; found 152.2 [M+H]⁺.

B-3—2,2,2-trifluoro-N-(2-(4-fluorophenyl)cyclopropyl)-N-(piperidin-4-ylmethyl)acetamide hydrochloride

Step 1: tert-butyl4-((2,2,2-trifluoro-N-(2-(4-fluorophenyl)cyclopropyl)acetamido)methyl)piperidine-1-carboxylate-XXX

To a stirred solution of 2-(4-fluorophenyl)cyclopropan-1-aminehydrochloride (XXVIII, 0.5 g, 2.66 mmol) in methanol (20 mL) was addedtert-butyl 4-formylpiperidine-1-carboxylate (0.57 g, 2.66 mmol) andsodium bicarbonate (0.20 g, 2.30 mmol) and molecular sieves (approx. 1g) at room temperature and the resulting mixture was heated to refluxfor 2 h. Cooled to 0° C., then sodium borohydride (0.1 g, 2.66 mmol) wasadded and stirred at room temperature for 1 h. Ice was added and thereaction mixture was filtered. The solvent was evaporated to get theresidue. Water was added and extracted with ethylacetate (2×100 mL). Theorganic portion was washed with water, brine, dried over sodium sulphateand concentrated under reduced pressure to afford the crude compound. Toa stirred solution of crude compound in dry dichloromethane (20 mL) wasadded TEA (0.92 mL, 6.65 mmol) and then cooled to 0° C. Thentrifluoroacetic anhydride (0.56 mL, 3.99 mmol) was added drop-wisecautiously and the resulting mixture was stirred for 2 h at thattemperature. The progress of the reaction was monitored by TLC. Thereaction mixture was diluted with dichloromethane and the organicportion was washed with water, brine solution, dried over sodiumsulphate and concentrated under reduced pressure to get the crudeproduct which was further purified by column chromatography usingethylacetate-hexane gradient to afford the titled product as browncolour sticky oil (XXX, 1.1 g, 93%). LC-MS m/z calcd for C₂₂H₂₈F₄N₂O₃,444.2; found 445.2 [M+H]⁺.

Step 2:2,2,2-trifluoro-N-(2-(4-fluorophenyl)cyclopropyl)-N-(piperidin-4-ylmethyl)acetamidehydrochloride-Intermediate B-3

To a stirred solution of tert-butyl4-((2,2,2-trifluoro-N-(2-(4-fluorophenyl)cyclopropyl)acetamido)methyl)piperidine-1-carboxylate(XXX, 1.1 g, 2.40 mmol) in dioxane (3 mL) was added 20% HCl in dioxane(3 mL) at 0° C. and stirred for 3 h at room temperature. The reactionmixture was concentrated under vacuum and triturated with diethyl ether.The resultant solid was dried under vacuum to afford the title productas off-white solid (B-3, 0.8 g, 94%). LC-MS m/z calcd for C₁₇H₂₀F₄N₂O,344.1; found 345.1 [M+H]⁺.

B-4—N-(azetidin-3-ylmethyl)-2,2,2-trifluoro-N-(2-(4-fluorophenyl)cyclopropyl)acetamide

Step 1:tert-butyl3-((2,2,2-trifluoro-N-(2-(4-fluorophenyl)cyclopropyl)acetamido)methyl)azetidine-1-carboxylate-XXXII

To a stirred solution of 2-(4-fluorophenyl)cyclopropan-1-aminehydrochloride (1.2 g, 6.41 mmol) in methanol (20 mL) was addedtert-butyl 3-formylazetidine-1-carboxylate (XXXI, 1.2 g, 6.41 mmol) andsodium bicarbonate (0.48 g, 5.77 mmol) and molecular sieves (approx. 1g) at room temperature and the resulting mixture was heated to refluxfor 2 h. Cooled to 0° C., then sodium borohydride (0.24 g, 6.41 mmol)was added and stirred at room temperature for 1 h. Ice was added and thereaction mixture was filtered. The solvent was evaporated to get theresidue. Water was added and extracted with ethylacetate (2×100 mL). Theorganic portion was washed with water, brine, dried over sodium sulphateand concentrated under reduced pressure to afford the crude compound. Toa stirred solution of crude compound in dry dichloromethane (10 mL) wasadded triethylamine (2.2 mL, 16.02 mmol) and then cooled to 0° C. Thentrifluoroacetic anhydride (0.98 mL, 7.05 mmol) was added drop-wisecautiously and the resulting mixture was stirred at that temperature for2 h. The progress of the reaction was monitored by TLC. The reactionmixture was diluted with dichloromethane and the organic portion waswashed with water, brine solution, dried over sodium sulphate andconcentrated under reduced pressure to get the crude product which waspurified by column chromatography using ethylacetate-hexane gradient toafford the titled product as sticky oil (XXXII, 2.3 g, 86%). LC-MS m/zcalcd for C₂₀H₂₄F₄N₂O₃, 416.2; found 317.3 [M-Boc+H]⁺.

Step-2:N-(azetidin-3-ylmethyl)-2,2,2-trifluoro-N-(2-(4-fluorophenyl)cyclopropyl)acetamide TFA salt-Intermediate B-4

To solution of compound (XXXII, 2.3 g, mmole) in dichloromethane (2.5mL) was added TFA (2.5 mL) and stirred at room temperature for 3 h.Then, the reaction mixture was concentrated under vacuum. The resultantcrude product was triturated with diethyl ether and then dried undervacuum to afford the titled product as sticky oil (B-4, 1.8 g, 78%).LC-MS m/z calcd for C₁₅H₁₆F₄N₂O, 316.1; found 221.1 [M-TFA]⁺.

B-5:N-(azetidin-3-ylmethyl)-2,2,2-trifluoro-N-(2-(4-iodophenyl)cyclopropyl)acetamide

Intermediate B-5 was synthesized following procedure for synthesizingB-4 LC-MS m/z calcd for C₁₅H₁₆F₃IN₂O, 424.0; found 425.0 [M+1]⁺.

B-6—2-(4-((4-fluorobenzyl)oxy)phenyl)cyclopropan-1-amine

Step-1: (E)-methyl3-(4-((4-fluorobenzyl)oxy)phenyl)acrylate-XXXIII

To a stirred solution of (E)-methyl 3-(4-hydroxyphenyl)acrylate (5.1 g,28.6 mmol), in dry DMF (50 mL) was added 1-(bromomethyl)-4-fluorobenzene(6.5 g, 34.3 mmol) and potassium carbonate (11.86 g, 85.9 mmol) at roomtemperature and the resulting mixture was stirred at room temperaturefor 16 h. Ice water was added to it and then extracted with ethylacetate(3×50 mL). The combined organic extract was washed with water, brine,dried over sodium sulphate and concentrated under reduced pressure toafford the product as off-white solid (XXXIII, 8 g, 97%). LC-MS m/zcalcd for C₁₇H₁₅FO₃, 286.1; found 287.1 [M+H]⁺.

Step-2: methyl2-(4-((4-fluorobenzyl)oxy)phenyl)cyclopropanecarboxylate-XXXIV

To a stirred solution of (E)-methyl3-(4-((4-fluorobenzyl)oxy)phenyl)acrylate (2 g, 6.9 mmol) in diethylether (50 mL) was added Pd(OAc)₂ (0.31 g, 1.3 mmol) at 0° C. and stirredfor 20 min. A freshly prepared solution of diazomethane (30 eq) indiethyl ether was then added slowly and stirred at room temperature for16 h. The reaction mixture was filtered through celite bed and washedwith dichloromethane. The filtrate was evaporated under reduced pressureto get crude product which was purified by column chromatography usingethylacetate-hexane gradient to afford the titled product as an offwhite solid (XXXIV, 1.96 g, 94%). LC-MS m/z calcd for C₁₈H₁₇FO₃, 300.1;found 301.1 [M+H]⁺.

Step-3:2-(4-((4-fluorobenzyl)oxy)phenyl)cyclopropanecarboxylicacid-XXXV

To a stirred solution of methyl2-(4-((4-fluorobenzyl)oxy)phenyl)cyclopropanecarboxylate (1.86 g, 6.2mmol) in tetrahydrofuran (10 mL) and methanol (10 mL) was added lithiumhydroxide (0.52 g, 12.4 mmol). The reaction mixture was heated at 50° C.for 12 h. The reaction was concentrated under vacuum and then acidifiedto pH 2 with 2N aqueous HCl. The resultant solid was filtered and driedunder vacuum to get the title product as a white colour solid (XXXV,1.65 g, 93%). LC-MS m/z calcd for C₁₇H₁₅FO₃, 286.1; found 285.1 [M−H].

Step-4: tert-butyl(2-(4-((4-fluorobenzyl)oxy)phenyl)cyclopropyl)carbamate-XXXVI

To a stirred solution of2-(4-((4-fluorobenzyl)oxy)phenyl)cyclopropanecarboxylic acid (XXXV, 1.74g, 6 mmol) in t-butanol (50 mL) was added triethylamine (1.26 mL, 9.10mmol) diphenylphosphorylazide (1.44 mL, 6.60 mmol) and then heated at80° C. for 48 h. The reaction mixture was concentrated under vacuum. Theresultant crude product was diluted with ethylacetate (100 mL) andwashed with water, brine, dried over sodium sulphate and concentratedunder reduced pressure which was purified by column chromatography usingethylacetate-hexane gradient to afford the titled product as yellowsolid (XXXVI, 1.05 g, 48%), LC-MS m/z calcd for C₂₁H₂₄FNO₃, 357.2; found358.2 [M+H]⁺.

Step-5:2-(4-((4-fluorobenzyl)oxy)phenyl)cyclopropanaminehydrochloride-B-6

To a stirred solution of tert-butyl(2-(4-((4-fluorobenzyl)oxy)phenyl)cyclopropyl)carbamate (XXXVI, 1.05 g,2.9 mmol) in 1,4-dioxane (10 mL) was added 20% HCl in 4-dioxane (10 mL)at 0° C. and then was heated at 50° C. for 3 h. The reaction mixture wasconcentrated under vacuum and the resultant solid was titurated withdiethyl ether. The solid was filtered and dried under vacuum to get thetitled product as white solid (B6, 0.76 g, 88%).

¹HNMR (400 MHz, DMSO-d₆): δ 8.39 (bs, 3H), 7.47-7.44 (m, 2H), 7.21-7.17(m, 2H), 7.07 (d, 2H, J=8.8 Hz), 6.91 (d, 2H, J=8.4 Hz), 5.04 (s, 2H),2.71-2.67 (m, 1H), 2.28-2.23 (m, 1H), 1.33-1.30 (m, 1H), 1.14-1.09 (m,1H). LC-MS m/z calcd for C₁₆H₁₆FNO, 257.1. found 258.2.

B-7—2-(4-(1-methyl-1H-pyrazol-3-yl)phenyl)cyclopropan-1-aminehydrochloride

Step 1:tert-butyl(2-(4-(1-methyl-1H-pyrazol-3-yl)phenyl)cyclopropyl)carbamate-XXXIX

To a stirred solution of tert-butyl(2-(4-iodophenyl)cyclopropyl)carbamate (XXXVII, 1 g, 2.78 mmol) inmixture of dimethoxyethane (8 mL) and water (0.5 mL) was added(1-methyl-1H-pyrazol-4-yl)boronic acid (0.42 g, 3.34 mmol) and potassiumcarbonate (0.76 g, 5.57 mmol) and then degassed for 5 min.1,1′-Bis(diphenylphosphino)ferrocene-palladium(II)dichloridedichloromethane complex (0.22 g, 0.27 mmol) was added and heated at 120°C. in microwave for 2 h. Water was added and extracted with ethylacetate(2×100 mL). The organic portion was washed with water, brine, dried oversodium sulphate and concentrated under reduced pressure to afford thecrude product which was purified by column chromatography usingmethanol-dichloromethane gradient to afford the titled product as stickyoil (XXXIX, 0.29 g, 40%), LC-MS m/z calcd for C₁₈H₂₃N₃O₂, 313.2; found214.2 [M-Boc+H]⁺.

Step 2: 2-(4-(1-methyl-1H-pyrazol-3-yl)phenyl)cyclopropan-1-aminehydrochloride-Intermediate B-7

To a stirred solution of tert-butyl(2-(4-(1-methyl-1H-pyrazol-3-yl)phenyl)cyclopropyl)carbamate (XXXIX,0.29 g, 1.11 mmol) in dioxane (15 mL) was added 20% HCl in dioxane (10mL) at 0° C. and stirred for 3 h at room temperature. The reactionmixture was concentrated under vacuum to afford the title product asoff-white solid (I-23, 0.18 g, 50%), LC-MS m/z calcd for C₁₃H₁₅N₃,213.1; found 214.1 [M+H]⁺.

B-8—2-(4-(3,5-dimethylisoxazol-4-yl)phenyl)cyclopropan-1-aminehydrochloride

The above intermediate B-8 was synthesized by following the experimentprocedure of B-7. LC-MS m/z calcd for C₁₄H₁₆N₂O, 228.1; found 229.1[M+H]⁺.

B-9—4-(4-(2-aminocyclopropyl)phenyl)-1-methylpyridin-2(1H)-onehydrochloride

The intermediate B-9 was synthesized by following the experimentprocedure of B-7. LC-MS m/z calcd for C₁₅H₁₆N₂O, 240.1; found 241.1[M+H]⁺.

B-10: 2-(4′-chloro-[1,1′-biphenyl]-4-yl)cyclopropan-1-amine

The intermediate B-10 was synthesized by following the experimentprocedure of B-7. LC-MS m/z calcd for C₁₅H₁₄ClN, 243.1 found 244.1[M+H]⁺.

B-11—2-(4-(pyrimidin-5-yl)phenyl)cyclopropan-1-amine

The intermediate B-11 was synthesized by following the experimentprocedure of B-7. LC-MS m/z calcd for C₁₃H₁₃N₃, 211.1. found 212.1[M+H]⁺.

B-12—2-(4′-fluoro-[1,1′-biphenyl]-4-yl)cyclopropan-1-amine

The intermediate B-12 was synthesized by following the experimentprocedure of B-7. LC-MS m/z calcd for C₁₅H₁₄FN, 227.1; found228.1[M+H]⁺.

B-13: 2-(4′-cyano-[1,1′-biphenyl]-4-yl)cyclopropan-1-amine

The intermediate B-13 was synthesized by following the experimentprocedure of B-7. LC-MS m/z calcd for C₁₆H₁₄N₂, 234.1; found 235.1[M+H]⁺.

B-14: 2-(4-(6-(trifluoromethyl)pyridin-3-yl)phenyl)cyclopropan-1-amine

The intermediate B-14 was synthesized by following the experimentprocedure of B-7. LC-MS m/z calcd for C₁₅H₁₃F₃N₂, 278.1; found279.1[M+H]⁺.

B-15—2-(1-isopropyl-1H-pyrazol-4-yl)cyclopropan-1-amine

Step-1: ethyl (E)-3-(1-isopropyl-1H-pyrazol-4-yl)acrylate-XLI

To a stirred solution of triethylphosphonoacetate (7.75 mL, 39.13 mmol)in tetrahydrofuran (80 mL) was added 60% of sodium hydride (0.94 g,39.13 mmol) at 0° C. and then stirred for 1 h.1-Isopropyl-1H-pyrazole-4-carbaldehyde (XL, 4.5 g, 32.57 mmol) intetrahydrofuran (20 mL) was added and stirred for 2 h at roomtemperature. The reaction mixture was quenched with ice-water. Then thereaction mixture was concentrated under vacuum. The resultant crude wasdiluted with ethylacetate (100 mL) and washed with water, brine, driedover sodium sulphate and concentrated under reduced pressure to resultin crude product which was purified by column chromatography usingethylacetate-hexane gradient to afford the titled product as colourlessoil (XLI, 5.4 g, 80% yield). LC-MS m/z calcd for C₁₁H₁₆N₂O₂, 208.1;found 209.1 [M+H]⁺.

Step-2: ethyl2-(1-isopropyl-1H-pyrazol-4-yl)cyclopropane-1-carboxylate-XLII

To a stirred solution of ethyl(E)-3-(1-isopropyl-1H-pyrazol-4-yl)acrylate (XLI, 0.5 g, 2.40 mmol) indiethyl ether (10 mL) was added Pd(OAc)₂ (0.026 g, 0.12 mmol) at 0° C.and stirred for 20 min. A freshly prepared solution of diazomethane (30eq.) in diethyl ether was then added slowly and stirred at roomtemperature for 16 h. The reaction mixture was filtered through celitebed and washed with dichloromethane. The filtrate was evaporated underreduced pressure to get crude product which was purified by columnchromatography using ethylacetate-hexane gradient to afford the titledproduct as an off-white solid (XLII, 0.37 g, 69%). LC-MS m/z calcd forC₁₂H₁₈N₂O₂, 222.1; found 223.1 [M+H]⁺.

Step-3:2-(1-isopropyl-1H-pyrazol-4-yl)cyclopropane-1-carboxylicacid-XLIII

To a stirred solution of ethyl2-(1-isopropyl-1H-pyrazol-4-yl)cyclopropane-1-carboxylate (XLII, 0.37 g,1.78 mmol) in water (8 mL) and methanol (2 mL) was added sodiumhydroxide (0.28 g, 7.11 mmol). The reaction mixture was stirred at roomtemperature for 2 h. The reaction was concentrated under vacuum and thenacidified to pH 5 with 2N aqueous HCl. The resultant stick solid wasextracted with dichloromethane (50 mL×3). The combined organic layer waswashed with brine solution and concentrated under vacuum to get thetitle product as colourless sticky oil (XLIII, 0.3 g, 87%). LC-MS m/zcalcd for C₁₀H₁₄N₂O₂, 194.1; found 195.1 [M+H]⁺.

Step-4: tert-butyl(2-(1-isopropyl-1H-pyrazol-4-yl)cyclopropyl)carbamate-XLIV

To a stirred solution of2-(1-isopropyl-1H-pyrazol-4-yl)cyclopropane-1-carboxylic acid (XLIII,0.3 g, 1.55 mmol) in t-butanol (10 mL) was added triethylamine (0.65 mL,4.64 mmol) diphenylphosphorylazide (0.5 mL, 2.32 mmol) and then heatedat 80° C. for 18 h. The reaction mixture was concentrated under vacuum.The resultant crude was diluted with ethylacetate (100 mL) and washedwith water, brine solution, dried over sodium sulphate and concentratedunder reduced pressure to result in crude product which was purified bycolumn chromatography using ethylacetate-hexane gradient to afford thetitled product as yellow solid (XLIV, 0.13 g, 33%). LC-MS m/z calcd forC₁₄H₂₃N₃O₂, 265.2; found 266.2 [M+H]⁺.

Step-5: 2-(1-isopropyl-1H-pyrazol-4-yl)cyclopropan-1-aminehydrochloride-B15

To a stirred solution of tert-butyl(2-(1-isopropyl-1H-pyrazol-4-yl)cyclopropyl)carbamate (XLIV, 0.13 g,0.49 mmol) in 1,4-dioxane (3 mL) was added 20% HCl in 1,4-dioxane (3 mL)at 0° C. and then was heated at room temperature for 3 h. The reactionmixture was concentrated under vacuum and the resultant solid wastiturated with diethyl ether. The solid was filtered out and dried undervacuum to get the titled product as white solid (B-15, 0.06 g, 61%).LC-MS m/z calcd for C₉H₁₅N₃, 165.1; found 166.1 [M+H]⁺.

B-16—2-(1-phenyl-1H-pyrazol-4-yl)cyclopropan-1-amine

The intermediate B-16 was synthesized starting from1-phenyl-1H-pyrazole-4-carbaldehyde by following the experimentprocedure of B-15. LC-MS m/z calcd for C₁₂H₁₃N₃, 199.1; found 200.1[M+H]⁺.

B-17—2-(2-methylthiazol-5-yl)cyclopropan-1-amine

The intermediate B-17 was synthesized starting from2-methylthiazole-5-carbaldehyde by following the experiment procedure ofB-15. LC-MS m/z calcd for C₇H₁₀N₂S, 154.0; found 155.1[M+H]⁺.

B-18—2-(pyridin-3-yl)cyclopropan-1-amine

Step-1: (E)-N-methoxy-N-methyl-3-(pyridin-3-yl)acrylamide-XLVI

To a stirred solution of (E)-3-(pyridin-3-yl)acrylic acid (XLV, 10 g,67.1 mmol) and N,O-dimethylhydroxylamine hydrochloride (13 g, 134 mmol)in DMF (300 mL) was added EDC.HCl (16.6 g, 87.1 mmol), HOBt (9 g, 67mmol) and TEA (46 mL, 335 mmol) at 0° C. and the resulting mixture wasstirred at room temperature for 16 h. The reaction mixture wasconcentrated under vacuum. The resultant crude was diluted withethylacetate and washed with water, brine, dried over sodium sulphateand concentrated under reduced pressure to get the crude product whichwas purified by column chromatography using methanol-dichloromethanegradient to afford the titled product as an sticky oil (XLVI, 8.2 g,64%). LC-MS m/z calcd for C₁₀H₁₂N₂O₂, 192.0; found 193.1 [M+H]⁺.

Step-2:N-methoxy-N-methyl-2-(pyridin-3-yl)cyclopropane-1-carboxamide-XLVII

To a stirred solution of trimethylsulfoxonium iodide (2.75 g, 12.5 mmol)in dry dimethyl sulfoxide (20 mL) was added 60% of sodium hydride (12.5g, 12.5 mmol) portion-wise at room temperature and then stirred for 3 h.(E)-N-methoxy-N-methyl-3-(pyridin-3-yl)acrylamide (1.2 g, 6.25 mmol) indimethyl sulfoxide (10 mL) was added and stirred for 2 h at roomtemperature. The reaction mixture was quenched with ice-water and thenextracted with ethylacetate. The combined organic layer was washed withwater, brine solution, dried over sodium sulphate and concentrated underreduced pressure which was purified by column chromatography usingethylacetate-hexane gradient to afford the titled product as colourlessoil (XLVII, 0.9 g, 70%), LC-MS m/z calcd for C₁₁H₁₄N₂O₂, 206.1; found207.1 [M+H]⁺.

Step-3: 2-(pyridin-3-yl)cyclopropane-1-carboxylic acid-XLVIII

To a stirred solution ofN-methoxy-N-methyl-2-(pyridin-3-yl)cyclopropane-1-carboxamide (XLVII,0.9 g, 4.3 mmol) in water (2 mL) and ethanol (1 mL) was added potassiumhydroxide (0.731 g, 13 mmol). The reaction mixture was stirred at roomtemperature for 16 h. The reaction was concentrated under vacuum andthen acidified to pH 5 with 2N aqueous HCl. The resultant crude wasconcentrated under vacuum and then methanol (5 mL) was added to it. Theresultant solid was filtrated and the filtrate was concentrated undervacuum to get the title product as colourless sticky oil (XLVIII, 0.45g, 64%). LC-MS m/z calcd for C₉H₉NO₂, 163.1; found 164.1 [M+H]⁺.

Step-4: tert-butyl (2-(pyridin-3-yl)cyclopropyl)carbamate-XLIX

To a stirred solution of 2-(pyridin-3-yl)cyclopropane-1-carboxylic acid(XLVIII, 0.4 g, 2.43 mmol) in t-butanol (20 mL) was added triethylamine(0.845 mL, 6.07 mmol), diphenylphosphorylazide (0.67 mL, 3.16 mmol) andthen heated at 80° C. for 18 h. The reaction mixture was concentratedunder vacuum. The resultant crude was diluted with ethylacetate (100 mL)and washed with water, brine solution, dried over sodium sulphate andconcentrated under reduced pressure which was purified by columnchromatography using ethylacetate-hexane gradient to afford the titledproduct as colourless sticky oil (XLIX, 0.11 g, 20%). LC-MS m/z calcdfor C₁₃H₁₈N₂O₂, 234.1; found 235.1 [M+H]⁺.

Step-5: 2-(pyridin-3-yl)cyclopropan-1-amine TFA salt-B-18

To a stirred solution of tert-butyl(2-(pyridin-3-yl)cyclopropyl)carbamate (XLIX, 0.05 g, 0.21 mmol) indichloromethane (1 mL) was added trifluoroacetic acid (0.5 mL) at 0° C.and then was stirred at room temperature for 3 h. The reaction mixturewas concentrated under vacuum and the resultant solid was titurated withdiethyl ether. The solid was filtered out and dried under vacuum to getthe titled product as cream colour solid (B-18, 0.03 g, 62%). LC-MS m/zcalcd for C₈H₁₀N₂, 134.1; found 135.1 [M+H]⁺.

B-19—5-(4-(2-aminocyclopropyl)phenyl)-1-methylpyridin-2(1H)-onehydrochloride

Step 1:tert-butyl(2-(4-(6-methoxypyridin-3-yl)phenyl)cyclopropyl)carbamate-LI

To a stirred solution of tert-butyl(2-(4-iodophenyl)cyclopropyl)carbamate (L, 1 g, 2.78 mmol) in mixture ofdimethoxyethane (8 mL) and water (2 mL) was added(6-methoxypyridin-3-yl)boronic acid (0.47 g, 3.06 mmol) and potassiumcarbonate (0.77 g, 5.56 mmol) and then degassed for 5 min.Tetrakis(triphenylphosphine)palladium(0) (0.16 g, 1.39) was added andheated at 60° C. for 2 h. Water was added and extracted withethylacetate (2×100 mL). The organic portion was washed with water,brine, dried over sodium sulphate and concentrated under reducedpressure to afford the crude product which was purified by columnchromatography using methanol-dichloromethane to afford the titledproduct as sticky oil (LI, 0.84 g, 89%). LC-MS m/z calcd for C₂₀H₂₄N₂O₃,340.2; found 341.2 [M+H]⁺.

Step 2: tert-butyl(2-(4-(1-methyl-6-oxo-1,6-dihydropyridin-3-yl)phenyl)cyclopropyl)carbamate-LII

To a stirred solution of tert-butyl(2-(4-(6-methoxypyridin-3-yl)phenyl)cyclopropyl)carbamate (LI, 0.85 g,2.5 mmol) in acetonitrile (5 mL) was added methyl iodide (1.5 mL) andheated at 60° C. for 16 h. The reaction mixture concentrated underreduced pressure and the resultant crude product was tritutrated withdiethyl ether to afford the titled product as light brown solid (LII,0.80 g, 94%). LC-MS m/z calcd for C₂₀H₂₄N₂O₃, 340.2; found 341.2 [M+H]⁺.

Step 3: 5-(4-(2-aminocyclopropyl)phenyl)-1-methylpyridin-2(1H)-onehydrochloride-B-19

To a stirred solution of tert-butyl(2-(4-(1-methyl-6-oxo-1,6-dihydropyridin-3-yl)phenyl) cyclopropyl)carbamate (LII, 0.85 g, 2.5 mmol) in dioxane (5 mL) was added 20% HCl indioxane (3 mL) at 0° C. and heated at 60° C. for 16 h. The reactionmixture was concentrated under vacuum to afford the title product asoff-white solid (B-19, 0.47 g, 68%). LC-MS m/z calcd for C₁₅H₁₆N₂O,240.1; found 241.1 [M+H]⁺.

B-20—5-(2-aminocyclopropyl)-1,3,3-trimethylindolin-2-one hydrochloride

Step-1: 5-bromoindolin-2-one-LIV

To a stirred suspension of indolin-2-one (LIII, 4.0 g, 27.0 mmol) inacetonitrile (160 mL), N-bromosuccinimide (6.24 g, 35.1 mmol) was addedportion-wise at 0° C. under nitrogen atmosphere and then stirred for 3 hat 15-20° C. The reaction mixture was quenched with ice-water (100 mL)to afford solid. The resultant solid was filtered through sinteredfunnel, washed with water and dried to afford the title compound as asolid (LIV, 6.0 g, 93%). LC-MS m/z calcd for C₈H₆BrNO, 210.9; found212.0. [M+H]⁺.

Step 2: 5-Bromo-1,3,3-trimethylindolin-2-one-LV

To a stirred solution of 5-bromoindolin-2-one (LIV, 7.25 g, 34.36 mmol)in tetrahydrofuran (70 mL) under nitrogen atmosphere, was added sodiumhydride (5.9 g, 137.0 mmol) portion-wise at 0° C. After addition ofsodium hydride, the reaction was stirred at room temperature for 30 min,then cooled to 0° C. Methyl iodide (8.5 mL, 137.0 mmol) was added, andthen allowed to stir at room temperature for 2 h. The reaction mass wascooled to 0° C. and carefully quenched with ice-water. Then the reactionmixture was diluted with water (150 mL) and ethylacetate (150 mL). Theorganic layer was separated, washed with water, brine solution, driedover sodium sulphate and concentrated under reduced pressure to affordthe titled product as brown colour solid (LV, 7.4 g, 85%). LC-MS m/zcalcd for C₁₁H₁₂BrNO, 253.0; found 254.0 [M+H]⁺.

Step-3: (E)-ethyl 3-(1,3,3-trimethyl-2-oxoindolin-5-yl)acrylate-LVI

To a stirred solution of 5-Bromo-1,3,3-trimethylindolin-2-one (LV, 9.0g, 35.0 mmol) in triethylamine (25 mL) was addedTetrakis(triphenylphosphine)palladium(0) (1.92 g, 1.75 mmol) and ethylacrylate (5.59 mL, 52.5 mmol). The reaction mixture was heated at 120°C. for 12 h. The reaction mass was cooled to room temperature and thendiluted with ethylacetate (50 mL). The reaction mixture was filtered outthrough with celite bed. The filtrate was washed with water (100 mL),1.5N HCl solution (100 mL), water (100 mL), dried over sodium sulphateand then concentrated under reduced pressure to afford the crude productwhich was purified by column chromatography using ethylacetate-hexanegradient to afford the titled product as yellow solid (LVI, 5.0 g, 70%).LC-MS m/z calcd for C₁₆H₁₉NO₃, 273.1; found 274.1 [M+H]⁺.

Step 4: ethyl2-(1,3,3-trimethyl-2-oxoindolin-5-yl)cyclopropanecarboxylate-LVII

To a stirred solution of (E)-ethyl,3-(1,3,3-trimethyl-2-oxoindolin-5-yl)acrylate (LVI, 2.0 g, 7.2 mmol) indiethyl ether (20 mL) was added Pd(OAc)₂ (0.32 g, 1.40 mmol), at 0° C.and stirred for 20 min. A freshly prepared diazomethane (30 eq) indiethyl ether was then added slowly and stirred at room temperature for16 h. The reaction mixture was filtered through celite bed and washedwith dichloromethane. The filtrate was evaporated under reduced pressureto get crude product which was purified by column chromatography usingethylacetate-hexane gradient to afford the titled product as an offwhite solid (LVII, 1.74 g, 82%). LC-MS m/z calcd for C₁₇H₂₁NO₃, 287.1;found 288.1 [M+H]⁺.

Step-5:2-(1,3,3-trimethyl-2oxoindolin-5-yl)cyclpropanecarboxylicacid-LVIII

To a stirred solution of ethyl2-(1,3,3-trimethyl-2-oxoindolin-5-yl)cyclopropanecarboxylate (LVII, 1.7g, 14.0 mmol) in tetrahydrofuran (5 mL), methanol (5 mL) and water (2mL) was added lithium hydroxide (0.62 g, 14.0 mmol). The reactionmixture was heated at 50° C. for 12 h. The reaction was concentratedunder vacuum and then acidified to pH 2 with aqueous solution of 2N HCl.The resultant solid was filteried and dried under vacuum to get thetitle product as a white colour solid (LVIII, 1.2 g, 79%). LC-MS m/zcalcd for C₁₅H₁₇NO₃, 259.1; found 260.1 [M+H]⁺.

Step-6: tert-butyl(2-(1,3,3-trimethyl-2-oxoindolin-5-yl)cyclopropyl)carbamate-LIX

To a stirred solution of2-(1,3,3-trimethyl-2oxoindolin-5-yl)cyclpropanecarboxylicacid (LVIII,3.0 g, 11.50 mmol) in t-butanol (200 mL) was added triethylamine (2.32mL, 17.2 mmol) diphenylphosphoryl azide (2.86 mL, 12.6 mmol) and thenheated at 80° C. for 48 h. The reaction mixture was concentrated undervacuum to afford the crude product which was purified by columnchromatography using ethylacetate-hexane gradient to afford the titledproduct as yellow solid (LIX, 2.5 g, 65%). LC-MS m/z calcd forC₁₉H₂₆N₂O₃, 330.2; found 331.2 [M+H]⁺.

Step-7: 5-(2-aminocyclopropyl)-1,3,3-trimethylindolin-2-one hydrochloricacid-B-20

To a stirred solution of tert-butyl(2-(1,3,3-trimethyl-2-oxoindolin-5-yl)cyclopropyl)carbamate (LIX, 12 g,51.0 mmol) in 1,4-dioxane (50 mL) was added 20% HCl in 4-dioxane (36 mL)at 0° C. and then was heated at 50° C. for 3 h. The reaction mixture wasconcentrated under vacuum and the resultant solid was titurated withdiethyl ether. The solid was filtered out and dried under vacuum to getthe titled product as white solid (B-20, 7.7 g, 87%). LC-MS m/z calcdfor C₁₄H₁₈N₂O, 230.1; found 231.1 [M+H]⁺.

B-21—2,2,2-trifluoro-N-(2-phenylcyclopropyl)-N-(2-azaspiro[3.3]heptan-6-yl)acetamidehydrochloride

Step-1: tert-butyl6-(2,2,2-trifluoro-N-(2-phenylcyclopropyl)acetamido)-2-azaspiro[3.3]heptane-2-carboxylate-LX

To a stirred solution of 2-phenylcyclopropan-1-amine hydrochloride(XXVIII, 0.2 g, 1.17 mmol) and tert-butyl6-oxo-2-azaspiro[3.3]heptane-2-carboxylate (0.3 g, 1.41 mmol) in DCE (6mL) was added sodium triacetoxyborohydride (0.89 g, 4.20 mmol) andstirred at room temperature for 0.5 h. Methanol (1 mL) was added andthen followed by addition of ethylacetate (10 mL) and 1M potassiumcarbonate solution and the stirring was continued for 30 min. Theorganic layer was separated and washed with water, brine solution, driedover sodium sulphate and concentrated under reduced pressure to get thecrude. The crude product was diluted with dry dichloromethane (5 mL) andcooled to 0° C. Triethylamine (0.5 mL, 3.51 mmol) and trifluoroaceticanhydride (0.25 mL, 1.70 mmol) were added to it. The reaction mixturewas stirred for 30 min. The reaction mixture was diluted withdichloromethane (50 mL) and washed with water, brine solution, driedover sodium sulphate and concentrated under reduced pressure to getcrude which was purified by column chromatography usingethylacetate-hexane gradient to afford the titled product as an browncolour liquid (LX, 0.2 g, 40%). LC-MS m/z calcd for C₂₂H₂₇F₃N₂O₃, 424.2;found 425.2 [M+H]⁺.

Step-2:2,2,2-trifluoro-N-(2-phenylcyclopropyl)-N-(2-azaspiro[3.3]heptan-6-yl)acetamidehydrochloride-Intermediate B-21

To a stirred solution of tert-butyl6-(2,2,2-trifluoro-N-(2-phenylcyclopropyl)acetamido)-2-azaspiro[3.3]heptane-2-carboxylate(LX, 0.2 g, 0.47 mmol) in 1,4-dioxane (2 mL) was added 20% HCl in1,4-dioxane (5 mL) and then was refluxed for 10 min. The reactionmixture was concentrated under vacuum and the resultant solid wastiturated with diethyl ether. The solid was filtered out and dried undervacuum to get the titled product B-21 as white solid (0.15 g, 98%).LC-MS m/z calcd for C₁₇H₁₉F₃N₂O, 324.1; found 325.1 [M+H]⁺.

B-22—N-(azetidin-3-ylmethyl)-2,2,2-trifluoro-N-(2-(4′-fluoro-[1,1′-biphenyl]-4-yl)cyclopropyl)acetamidehydrochloride

The intermediate B-22 was synthesized starting from intermediate B-12following procedure given for the synthesis of B-4. LC-MS m/z calcd forC₂₁H₂₀F₄N₂O, 392.1; found 393.1 [M+H]⁺.

B-23—N-(azetidin-3-ylmethyl)-2,2,2-trifluoro-N-(2-(4-(1-methyl-1H-pyrazol-4-yl)phenyl)cyclopropyl)acetamidehydrochloride

The intermediate B-23 was synthesized starting from intermediate B-7following procedure given for the synthesis of B-4. LC-MS m/z calcd forC₁₉H₂₁F₃N₄O, 378.1; found 379.1 [M+H]⁺.

B-24—N-(azetidin-3-ylmethyl)-N-(2-(4-(3,5-dimethylisoxazol-4-yl)phenyl)cyclopropyl)-2,2,2-trifluoroacetamidehydrochloride

The intermediate B-24 was synthesized starting from intermediate B-8following procedure given for the synthesis of B-4. LC-MS m/z calcd forC₂₀H₂₂F₃N₃O₂, 393.1; found 394.2 [M+H]⁺.

B-25—N-((1-(2-aminoethyl)piperidin-4-yl)methyl)-2,2,2-trifluoro-N-(2-(4-fluorophenyl)cyclopropyl)acetamidehydrochloride

Step 1: tert-butyl(2-(4-((2,2,2-trifluoro-N-(2-(4-fluorophenyl)cyclopropyl)acetamido)methyl)piperidin-1-yl)ethyl)carbamate-LXI

To a solution of2,2,2-trifluoro-N-(2-(4-fluorophenyl)cyclopropyl)-N-(piperidin-4-ylmethyl)acetamidehydrochloride (B-3, 0.5 g, 1.40 mmol) in acetonitrile (5 mL) was addedtert-butyl (2-bromoethyl)carbamate (0.35 g, 1.50 mmol) andN,N-diisopropylethylamine (0.75 mL, 4.2 mmol). Then the reaction mixturewas heated at 50° C. for 16 h. After completion of reaction, thereaction was diluted with ethylacetate (50 mL), washed with water, brinesolution, dried over sodium sulfate and concentrated under vacuum toafford the crude product which was further purified by flashchromatography using methanol-dichloromethane gradient to result in thetitled product as a brown colour liquid (LXI, 0.6 g, 85%). LC-MS m/zcalcd for C₂₄H₃₃F₄N₃O₃, 487.2; found 488.2 [M+H]⁺.

Step 2:N-((1-(2-aminoethyl)piperidin-4-yl)methyl)-2,2,2-trifluoro-N-(2-(4-fluorophenyl)cyclopropyl)acetamidehydrochloride-B-25

To a stirred solution of tert-butyl(2-(4-((2,2,2-trifluoro-N-(2-(4-fluorophenyl)cyclopropyl)acetamido)methyl)piperidin-1-yl)ethyl)carbamate(LXI, 0.6 g, 1.20 mmol) in dioxane (5 mL) was added 20% HCl in dioxane(3 mL) at 0° C. and stirred for 2 h at room temperature. The reactionmixture was concentrated under vacuum and triturated with diethyl ether.The resultant solid was dried under vacuum to afford the title productas off-white solid (B-25, 0.48 g, quantitative yield). LC-MS m/z calcdfor C₁₉H₂₅F₄N₃O, 387.2; found 388.2 [M+H]⁺.

B-26—N-((1-(2-aminoethyl)piperidin-4-yl)methyl)-2,2,2-trifluoro-N-(2-phenylcyclopropyl)acetamidehydrochloride

The intermediate B-26 was synthesized starting from2,2,2-trifluoro-N-(2-phenylcyclopropyl)-N-(piperidin-4-ylmethyl)acetamideand tert-butyl (2-bromoethyl)carbamate by following the experimentprocedure of -B-25. LC-MS m/z calcd for C₁₉H₂₆F₃N₃O, 369.2; found 370.1[M+H]⁺.

B-27—N-((1-(2-aminoethyl)piperidin-4-yl)methyl)-N-(2-(3,4-difluorophenyl)cyclopropyl)-2,2,2-trifluoroacetamide hydrochloride

The intermediate B-27 was synthesized starting fromN-(2-(3,4-difluorophenyl)cyclopropyl)-2,2,2-trifluoro-N-(piperidin-4-ylmethyl)acetamideand tert-butyl (2-bromoethyl)carbamate by following the experimentprocedure of -B-25. LC-MS m/z calcd for C₁₉H₂₂F₅N₂O, 389.2; found 390.1[M+H]⁺.

Synthesis of Intermediate Esters-I Series I-2(E)-3-[4-({tert-Butoxycarbonyl-[2-(4-fluoro-phenyl)-cyclopropyl]-amino}-methyl)-phenyl]-acrylicacid methyl ester (LXII)

Step 1:(E)-3-(4-{[2-(4-Fluoro-phenyl)-cyclopropylamino]-methyl}-phenyl)-acrylicacid methyl ester ( )

To a stirred solution of 2-(4-fluoro-phenyl)-cyclopropylaminehydrochloride (XXVIII, 0.2 g, 1.06 mmol) in methanol (20 mL) was added(E)-3-(4-formyl-phenyl)-acrylic acid methyl ester (0.24 g, 1.28 mmol)and sodium bicarbonate (0.08 g, 0.95 mmol) and molecular sieves (approx1 g) at room temperature and the resulting mixture was heated to refluxfor 2.5 h. Cooled to 0° C. and sodium borohydride (0.036 g, 0.95 mmol)was added, stirred at room temperature for 1 h. Ice was added and thereaction mixture was filtered. The solvent was evaporated to get theresidue. Water was added and extracted with dichloromethane (2×50 mL).The organic portion was washed with water and brine dried over sodiumsulphate and concentrated under reduced pressure to afford the crudeproduct which was purified by column chromatography usingmethanol-dichloromethane gradient to afford the titled product as yellowoil. (LXII, 0.3 g, 90%). LC-MS m/z calcd for C₂₀H₂₀FNO₂, 325.1; found326.3 [M+H]⁺.

Step 2:(E)-3-[4-({tert-Butoxycarbonyl-[2-(4-fluoro-phenyl)-cyclopropyl]-amino}-methyl)-phenyl]-acrylicacid methyl ester (I-2)

To a stirred solution of(E)-3-(4-{[2-(4-fluoro-phenyl)-cyclopropylamino]-methyl}-phenyl)-acrylicacid methyl ester (XLVI, 0.25 g, 0.76 mmol) in tetrahydrofuran and watermixture (6 mL, 1:1) was added sodium bicarbonate (0.087 g, 2.3 mmol) andBoc anhydride (0.22 mL, 0.92 mmol) at room temperature and the resultingmixture was stirred at that temperature for 2 h. The progress of thereaction was monitored by TLC. The reaction mixture was diluted withethylacetate and the organic portion was washed with water and brinesolution, dried over sodium sulphate and concentrated under reducedpressure to get the crude product which was purified by columnchromatography using ethylacetate-hexane gradient to afford the titledproduct as sticky oil (I-2, 0.19 g, 58%). LC-MS m/z calcd forC₂₅H₂₈FNO₄, 425.2; found 326.3 [M-Boc+1]⁺.

The following compounds were synthesized using procedure for thesynthesize of I-2

I-3methyl(E)-3-(4-(((tert-butoxycarbonyl)(2-(4-((4-fluorobenzyl)oxy)phenyl)cyclopropyl)amino)methyl)phenyl)acrylate

The compound was synthesized using amine B6 and(E)-3-(4-Formyl-phenyl)-acrylic acid methyl ester following theprocedure for the synthesis of I-2. LC-MS m/z calcd for C₃₂H₃₄FNO₅,531.2; found 532.2 [M+H]⁺.

I-4 methyl(E)-3-(4-(4-(((tert-butoxycarbonyl)(2-phenylcyclopropyl)amino)methyl)piperidin-1-yl)phenyl)acrylate

The compound was synthesized using phenylcyclopropyl amine and aldehydeA2 following the procedure for the synthesis of I-2. LC-MS m/z calcd forC₃₀H₃₈N₂O₄, 490.3; found 434.2 [M-56]⁺.

I-5 methyl(E)-3-(4-(((tert-butoxycarbonyl)(2-(4′-chloro-[1,1′-biphenyl]-4-yl)cyclopropyl)amino)methyl)phenyl)acrylate

The compound was synthesized using amine B10 and methyl-4-formylcinnamic acid ester following the procedure for the synthesis of I-2.LC-MS m/z calcd for C₃₁H₃₂ClNO₄, 517.2; found 462.2 [M-56]⁺.

I-6 methyl(E)-3-(4-(((tert-butoxycarbonyl)(2-(4-(3,5-dimethylisoxazol-4-yl)phenyl)cyclopropyl)amino)methyl)phenyl)acrylate

The compound was synthesized using amine B8 and methyl-4-formyl cinnamicacid ester following the procedure for the synthesis of I-2. LC-MS m/zcalcd for C₃₀H₃₄N₂O₅, 502.2; found 503.2 [M+H]⁺.

I-7 methyl(E)-3-(4-(((tert-butoxycarbonyl)(2-(4-(pyrimidin-5-yl)phenyl)cyclopropyl)amino)methyl)phenyl)acrylate

The compound was synthesized using amine B11 and methyl-4-formylcinnamic acid ester following the procedure for the synthesis of I-2.LC-MS m/z calcd for C₂₉H₃₁N₃O₄, 485.2; found 486.2 [M+H]⁺.

I-8 methyl2-(4-(((tert-butoxycarbonyl)(2-(4-fluorophenyl)cyclopropyl)amino)methyl)piperidin-1-yl)pyrimidine-5-carboxylate

The compound was synthesized using 4-fluorophenyl cyclopropyl amine andaldehyde A1 following the procedure for the synthesis of I-2. LC-MS m/zcalcd for C₂₆H₃₃FN₄O₄, 484.2; found 485.2 [M+H]⁺.

I-9 methyl2-(4-((tert-butoxycarbonyl)(2-phenylcyclopropyl)amino)piperidin-1-yl)pyrimidine-5-carboxylate

The compound was synthesized using phenylcyclopropyl amine and ketone A3following the procedure for the synthesis of I-2. LC-MS m/z calcd forC₂₅H₃₂N₄O₄, 452.2; found 453.2[M+H]⁺.

I-10 methyl2-(4-((tert-butoxycarbonyl)(2-(4-fluorophenyl)cyclopropyl)amino)piperidin-1-yl)pyrimidine-5-carboxylate

The compound was synthesized using 4-fluorophenylcyclopropyl amine andketone A3 following the procedure for the synthesis of I-2. LC-MS m/zcalcd for C₂₅H₃₁FN₄O₄, 470.2; found 471.2 [M+H]⁺.

I-11 methyl2-(4-(((tert-butoxycarbonyl)(2-(4-((4-fluorobenzyl)oxy)phenyl)cyclopropyl)amino)methyl)piperidin-1-yl)pyrimidine-5-carboxylate

The compound was synthesized using amine B-6 and aldehyde A1 followingthe procedure for the synthesis of I-2. LC-MS m/z calcd for C₃₃H₃₉FN₄O₅,590.3; found 591.2 [M+H]⁺.

I-12 methyl2-(4-((tert-butoxycarbonyl)(2-(4-((4-fluorobenzyl)oxy)phenyl)cyclopropyl)amino)piperidin-1-yl)pyrimidine-5-carboxylate

The compound was synthesized using amine B-6 and ketone A3 following theprocedure for the synthesis of I-2. LC-MS m/z calcd for C₃₂H₃₇FN₄O₅,576.2; found 577.3 [M+H]⁺.

I-13methyl2-(4-((tert-butoxycarbonyl)(2-(4′-chloro-[1,1′-biphenyl]-4-yl)cyclopropyl)amino)piperidin-1-yl)pyrimidine-5-carboxylate

The compound was synthesized using amine B-10 and ketone A3 followingthe procedure for the synthesis of I-2. LC-MS m/z calcd forC₃₁H₃₅ClN₄O₄, 562.2; found 563.2 [M+H]⁺.

I-14 methyl2-(4-(((tert-butoxycarbonyl)(2-(4′-chloro-[1,1′-biphenyl]-4-yl)cyclopropyl)amino)methyl)piperidin-1-yl)pyrimidine-5-carboxylate

The compound was synthesized using amine B-10 and aldehyde A1 followingthe procedure for the synthesis of I-2. LC-MS m/z calcd forC₃₂H₃₇ClN₄O₄, 576.2; found 577.2 [M+H]⁺.

I-15 ethyl2-(4-(((tert-butoxycarbonyl)(2-(4′-fluoro-[1,1′-biphenyl]-4-yl)cyclopropyl)amino)methyl)piperidin-1-yl)pyrimidine-5-carboxylate

The compound was synthesized using amine B-12 and aldehyde A1 followingthe procedure for the synthesis of I-2. LC-MS m/z calcd for C₃₃H₃₉FN₄O₄,574.3; found 575.3 [M+H]⁺.

I-16 methyl2-(4-(((tert-butoxycarbonyl)(2-(4-(3,5-dimethylisoxazol-4-yl)phenyl)cyclopropyl)amino)methyl)piperidin-1-yl)pyrimidine-5-carboxylate

The compound was synthesized using amine B-8 and aldehyde A1 followingthe procedure for the synthesis of I-2. LC-MS m/z calcd for C₃₁H₃₉N₅O₅,561.2; found 562.2 [M+H]⁺.

I-17 methyl2-(4-(((tert-butoxycarbonyl)(2-(4-(pyrimidin-5-yl)phenyl)cyclopropyl)amino)methyl)piperidin-1-yl)pyrimidine-5-carboxylate

The compound was synthesized using amine B-11 and aldehyde A1 followingthe procedure for the synthesis of I-2. LC-MS m/z calcd for C₃₀H₃₆N₆O₄,544.3. found 545.2 [M+H]⁺.

I-18 methyl2-(4-(((tert-butoxycarbonyl)(2-(4-methoxyphenyl)cyclopropyl)amino)methyl)piperidin-1-yl)pyrimidine-5-carboxylate

The compound was synthesized using 4-methoxyphenyl cyclopropyl amine andaldehyde A1 following the procedure for the synthesis of I-2. LC-MS m/zcalcd for C₂₇H₃₆N₄O₅, 496.2. found 497.3 [M+H]⁺.

I-19 methyl2-(4-((tert-butoxycarbonyl)(2-(4-methoxyphenyl)cyclopropyl)amino)piperidin-1-yl)pyrimidine-5-carboxylate

The compound was synthesized using 4-methoxyphenyl cyclopropyl amine andketone A3 following the procedure for the synthesis of I-2. LC-MS m/zcalcd for C₂₆H₃₄N₄O₅, 482.2. found 483.2 [M+H]⁺.

I-20 methyl2-(4-(((tert-butoxycarbonyl)((1R,2S)-2-(4-fluorophenyl)cyclopropyl)amino)methyl)piperidin-1-yl)pyrimidine-5-carboxylate

The compound was synthesized using 4-fluorophenyl cyclopropyl amine B1and aldehyde A1 following the procedure for the synthesis of I-2. LC-MSm/z calcd for C₂₆H₃₃FN₄O₄, 484.2. found 485.2 [M+H]⁺.

I-21 methyl2-(4-(((tert-butoxycarbonyl)((1S,2R)-2-(4-fluorophenyl)cyclopropyl)amino)methyl)piperidin-1-yl)pyrimidine-5-carboxylate

The compound was synthesized using 4-fluorophenyl cyclopropyl amine B2and aldehyde A1 following the procedure for the synthesis of I-2. LC-MSm/z calcd for C₂₆H₃₃FN₄O₄, 484.2. found 485.2 [M+H]⁺.

I-22 methyl4-(4-(((tert-butoxycarbonyl)(2-(4-fluorophenyl)cyclopropyl)amino)methyl)piperidin-1-yl)benzoate

The compound was synthesized using 4-fluorophenyl cyclopropyl amine andaldehyde A2 following the procedure for the synthesis of I-2. LC-MS m/zcalcd for C₂₈H₃₅FN₂O₄, 482.2. found 483.3 [M+H]⁺.

I-23 methyl2-(2-(((tert-butoxycarbonyl)(2-phenylcyclopropyl)amino)methyl)-5,6-dihydroimidazo[1,2-a]pyrazin-7(8H)-yl)pyrimidine-5-carboxylate

The compound was synthesized using phenylcyclopropyl amine and aldehydeA4 following the procedure for the synthesis of I-2. LC-MS m/z calcd forC₂₇H₃₂N₆O₄, 504.2. found 505.2 [M+H]⁺.

I-24 methyl2-(2-(((tert-butoxycarbonyl)(2-(4-methoxyphenyl)cyclopropyl)amino)methyl)-5,6-dihydroimidazo[1,2-a]pyrazin-7(8H)-yl)pyrimidine-5-carboxylate

The compound was synthesized using 4-methoxyphenylcyclopropyl amine andaldehyde A4 following the procedure for the synthesis of I-2. LC-MS m/zcalcd for C₂₈H₃₄N₆O₅, 534.2. found 535.2 [M+H]⁺.

I-25 methyl2-(2-(((tert-butoxycarbonyl)(2-(4-fluorophenyl)cyclopropyl)amino)methyl)-5,6-dihydroimidazo[1,2-a]pyrazin-7(8H)-yl)pyrimidine-5-carboxylate

The compound was synthesized using 4-fluorophenylcyclopropyl amine andaldehyde A4 following the procedure for the synthesis of I-2. LC-MS m/zcalcd for C₂₇H₃₁FN₆O₄, 522.2. found 523.2 [M+H]⁺.

I-26 methyl3-(((2-(4-bromophenyl)cyclopropyl)(tert-butoxycarbonyl)amino)methyl)benzoate

The compound was synthesized using 4-bromophenylcyclopropyl amine andmethyl-3-formyl benzoic acid ester following the procedure for thesynthesis of I-2. LC-MS m/z calcd for C₂₃H₂₆BrNO₄, 459.1. found 460.1[M+H]⁺.

I-27 methyl3-(((tert-butoxycarbonyl)(2-phenylcyclopropyl)amino)methyl)benzoate

The compound was synthesized using phenylcyclopropyl amine andmethyl-3-formyl benzoic acid ester following the procedure for thesynthesis of I-2. LC-MS m/z calcd for C₂₃H₂₇NO₄, 381.2. found 382.1[M+H]⁺.

I-28 methyl4-(((tert-butoxycarbonyl)(2-phenylcyclopropyl)amino)methyl)benzoate

The compound was synthesized using phenylcyclopropyl amine andmethyl-4-formyl benzoic acid ester following the procedure for thesynthesis of intermediate I-2. LC-MS m/z calcd for C₂₃H₂₇NO₄, 381.2.found 382.1 [M+H]⁺.

I-29 ethyl 6-((tert-butoxycarbonyl)(2-phenylcyclopropyl)amino)hexanoate

The compound was synthesized using phenylcyclopropyl amine and methyl6-oxohexanoate following the procedure for the synthesis of I-2. LC-MSm/z calcd for C₂₂H₃₃NO₄, 375.2. found 276.2 [M-BocH]⁺.

I-30 ethyl4-(3-((tert-butoxycarbonyl)(2-(4-fluorophenyl)cyclopropyl)amino)propyl)benzoate

The compound was synthesized using phenylcyclopropyl amine and methyl4-(3-oxopropyl)benzoate following the procedure for the synthesis ofI-2. LC-MS m/z calcd for C₂₆H₃₂FNO₄, 441.2. found 386.2 [M-55].

I-31 methyl7-(4-(((tert-butoxycarbonyl)(2-phenylcyclopropyl)amino)methyl)benzamido)heptanoate

The compound was synthesized using phenylcyclopropyl amine and aldehydeA5 following the procedure for the synthesis of I-2. LC-MS m/z calcd forC₃₀H₄₀N₂O₅, 508.3. found 509.3 [M+H]⁺.

I-32 methyl7-(4-(((tert-butoxycarbonyl)(2-(4-fluorophenyl)cyclopropyl)amino)methyl)benzamido)heptanoate

The compound was synthesized using 4-fluorophenylcyclopropyl amine andaldehyde A5 following the procedure for the synthesis of I-2. LC-MS m/zcalcd for C₃₀H₃₉FN₂O₅, 526.3. found 527.3 [M+H]⁺.

I-33 methyl4-((tert-butoxycarbonyl)(2-phenylcyclopropyl)amino)cyclohexanecarboxylate

The compound was synthesized using phenylcyclopropyl amine and methyl4-oxocyclohexane-1-carboxylate following the procedure for the synthesisof I-2. LC-MS m/z calcd for C₂₂H₃₁NO₄, 373.2. found 374.2 [M+H]⁺.

I-34 (1S,4R)-methyl4-((1S)-1-((tert-butoxycarbonyl)(2-phenylcyclopropyl)amino)ethyl)cyclohexanecarboxylate

The compound was synthesized using phenylcyclopropyl amine and methyl(1R,4R)-4-acetylcyclohexane-1-carboxylate following the procedure forthe synthesize of I-2 LC-MS m/z calcd for C₂₄H₃₅NO₄, 401.2. found 402.2[M+H]⁺.

I-35 methyl4-((4-(((tert-butoxycarbonyl)(2-(4-(1-methyl-6-oxo-1,6-dihydropyridin-3-yl)phenyl)cyclopropyl)amino)methyl)piperidin-1-yl)methyl)benzoate

The compound was synthesized using amine B19 and methyl4-((4-formylpiperidin-1-yl)methyl)benzoate following the procedure forthe synthesis of I-2. LC-MS m/z calcd for C₃₅H₄₃N₃O₅, 585.3. found 586.3[M+H]⁺.

I-36 methyl4-((4-(((tert-butoxycarbonyl)(2-phenylcyclopropyl)amino)methyl)piperidin-1-yl)methyl)benzoate

The compound was synthesized using Phenylcyclopropyl amine and methyl4-((4-formylpiperidin-1-yl)methyl)benzoate following the procedure forthe synthesis of I-2. LC-MS m/z calcd for C₂₉H₃₈N₂O₄, 478.3. found 479.3[M+H]⁺.

I-37 methyl4-((4-(((tert-butoxycarbonyl)(2-(4-(3,5-dimethylisoxazol-4-yl)phenyl)cyclopropyl)amino)methyl)piperidin-1-yl)methyl)benzoate

The compound was synthesized using amine B8 and methyl4-((4-formylpiperidin-1-yl)methyl)benzoate following the procedure forthe synthesis of I-2. LC-MS m/z calcd for C₃₄H₄₃N₃O₅, 573.3. found 574.3[M+H]⁺.

I-38 methyl4-((4-(((tert-butoxycarbonyl)(2-(4-(pyrimidin-5-yl)phenyl)cyclopropyl)amino)methyl)piperidin-1-yl)methyl)benzoate

The compound was synthesized using amine B11 and methyl4-((4-formylpiperidin-1-yl)methyl)benzoate following the procedure forthe synthesis of I-2. LC-MS m/z calcd for C₃₃H₄₀N₄O₄, 556.3. found 557.3[M+H]⁺.

I-39 methyl6-((4-(((tert-butoxycarbonyl)(2-(4-(3,5-dimethylisoxazol-4-yl)phenyl)cyclopropyl)amino)methyl)piperidin-1-yl)methyl)nicotinate

The compound was synthesized using amine B8 and methyl6-((4-formylpiperidin-1-yl)methyl)nicotinate following the procedure forthe synthesize of I-2. LC-MS m/z calcd for C₃₃H₄₂N₄O₅, 574.3. found575.3 [M+H]⁺.

I-40 ethyl4-((4-(((tert-butoxycarbonyl)(2-phenylcyclopropyl)amino)methyl)-1H-pyrazol-1-yl)methyl)benzoate

The compound was synthesized using Phenylcyclopropyl amine and aldehydeA12 following the procedure for the synthesis of I-2. LC-MS m/z calcdfor C₂₈H₃₃N₃O₄, 475.2. found 476.2 [M+H]⁺.

I-41 ethyl4-((4-(((tert-butoxycarbonyl)(2-phenylcyclopropyl)amino)methyl)-1H-1,2,3-triazol-1-yl)methyl)benzoate

The compound was synthesized using phenylcyclopropyl amine and aldehydeA7 following the procedure for the synthesis of I-2. LC-MS m/z calcd forC₂₇H₃₂N₄O₄, 476.2. found 477.2 [M+H]⁺.

I-42 methyl4-(2-(4-(((tert-butoxycarbonyl)(2-phenylcyclopropyl)amino)methyl)piperidin-1-yl)ethyl)benzoate

The compound was synthesized using Phenylcyclopropyl amine and aldehydeA15 following the procedure for the synthesis of I-2. LC-MS m/z calcdfor C₃₀H₄₀N₂O₄, 492.66. found 393.6 [M+H-Boc]⁺.

I-43 ethyl4-(3-(4-(((tert-butoxycarbonyl)(2-phenylcyclopropyl)amino)methyl)piperidin-1-yl)propyl)benzoate

The compound was synthesized using phenylcyclopropyl amine and aldehydeA19 following the procedure for the synthesis of I-2. LC-MS m/z calcdfor C₃₂H₄₄N₂O₄, 520.3. found 521.3 [M+H]⁺.

I-44 ethyl4-(3-(4-((tert-butoxycarbonyl)(2-phenylcyclopropyl)amino)piperidin-1-yl)propyl)benzoate

The compound was synthesized using phenylcyclopropyl amine and aldehydeA16 following the procedure for the synthesis of I-2. LC-MS m/z calcdfor C₃₁H₄₂N₂O₄, 506.3. found 507.3 [M+H]⁺.

I-46 ethyl4-(3-(6-(2,2,2-trifluoro-N-(2-phenylcyclopropyl)acetamido)-2-azaspiro[3.3]heptan-2-yl)propyl)benzoate

To a solution of2,2,2-trifluoro-N-(2-phenylcyclopropyl)-N-(2-azaspiro[3.3]heptan-6-yl)acetamidehydrochloride (B-21, 0.2 g, 0.5 mmol) in acetonitrile (2 mL) was addedethyl 4-(3-bromopropyl)benzoate (0.149 g, 0.5 mmol) andN,N-diisopropylethylamine (0.26 mL, 1.5 mmol). Then the reaction mixturewas heated at 60° C. for 16 h. After completion of reaction, thereaction was diluted with ethylacetate (50 mL), washed with water, brinesolution, dried over sodium sulfate and concentrated under vacuum to getcrude product which was purified by column chromatography usingethylacetate-hexane gradient to afford the titled product as brown gummysolid (I-46, 0.140 g, 49%). LC-MS m/z calcd for C₂₉H₃₃F₃N₂O₃, 514.2;found 515.3 [M+H]⁺.

I-47 ethyl4-(3-(4-(((tert-butoxycarbonyl)(2-(4-fluorophenyl)cyclopropyl)amino)methyl)piperidin-1-yl)propyl)benzoate

The compound was synthesized using 4-fluorophenylcyclopropyl amine andaldehyde A19 following the procedure for the synthesis of I-2. LC-MS m/zcalcd for C₃₂H₄₃FN₂O₄, 538.3. found 539.3 [M+H]⁺.

I-48 ethyl4-(3-(3-(((tert-butoxycarbonyl)(2-(4-fluorophenyl)cyclopropyl)amino)methyl)azetidin-1-yl)propyl)benzoate

The intermediate I-48 was synthesized using B-4 and ethyl4-(3-bromopropyl)benzoate following the procedure for the synthesis ofI-46. LC-MS m/z calcd for C₃₀H₃₉FN₂O₄, 510.3. found 511.3 [M+H]⁺.

I-49 ethyl4-(3-(4-(((tert-butoxycarbonyl)(2-(3-fluorophenyl)cyclopropyl)amino)methyl)piperidin-1-yl)propyl)benzoate

The compound was synthesized using 3-fluorophenylcyclopropyl amine andaldehyde A19 following the procedure for the synthesis of I-2. LC-MS m/zcalcd for C₃₂H₄₃FN₂O₄, 538.3. found 539.3 [M+H]⁺.

I-50 ethyl4-(3-(4-(((tert-butoxycarbonyl)(2-(3,4-difluorophenyl)cyclopropyl)amino)methyl)piperidin-1-yl)propyl)benzoate

The compound was synthesized using 3,4-difluorophenylcyclopropyl amineand aldehyde A19 following the procedure for the synthesis of I-2. LC-MSm/z calcd for C₃₂H₄₂F₂N₂O₄, 556.3. found 557.3 [M+H]⁺.

I-51 ethyl4-(3-(4-(((tert-butoxycarbonyl)(2-(4-methoxyphenyl)cyclopropyl)amino)methyl)piperidin-1-yl)propyl)benzoate

The compound was synthesized using 4-methoxyphenylcyclopropyl amine andaldehyde A19 following the procedure for the synthesis of I-2. LC-MS m/zcalcd for C₃₃H₄₆N₂O₅, 550.3. found 551.3 [M+H]⁺.

I-52 ethyl4-(3-(4-(((tert-butoxycarbonyl)(2-(4-((4-fluorobenzyl)oxy)phenyl)cyclopropyl)amino)methyl)piperidin-1-yl)propyl)benzoate

The compound was synthesized using amine B6 and aldehyde A19 followingthe procedure for the synthesis of I-2. LC-MS m/z calcd for C₃₉H₄₉FN₂O₅,644.3. found 645.4 [M+H]⁺.

I-53: ethyl4-(3-(4-(((tert-butoxycarbonyl)(2-(4-iodophenyl)cyclopropyl)amino)methyl)piperidin-1-yl)propyl)benzoate

Step-1

To a stirred solution of 2-(4-iodophenyl)cyclopropan-1-aminehydrochloride (LXIII, 1.0 g, 3.30 mmol) in methanol (50 mL) was addedethyl 4-(3-(4-formylpiperidin-1-yl)propyl)benzoate (I-3, 1.13 g, 3.30mmol) and sodium bicarbonate (0.25 g, 2.90 mmol) and molecular sieves(approx 2 g) at room temperature and the resulting mixture was heated toreflux for 2 h. Cooled to 0° C., then sodium borohydride (0.12 g, 3.30mmol) was added and stirred at room temperature for 1 h. Ice was addedand the reaction mixture was filtered. The solvent was evaporated to getthe residue. Water was added and extracted with ethylacetate (2×200 mL).The organic portion was washed with water, brine, dried over sodiumsulphate and concentrated under reduced pressure to afford the crudecompound. To a stirred solution of crude compound in mixture oftetrahydrofuran and water (20 mL, 1:1) was added sodium bicarbonate(0.69 g, 8.25 mmol) and Boc anhydride (1.05 mL, 4.90 mmol) at roomtemperature and the resulting mixture was stirred at that temperaturefor 2 h. The progress of the reaction was monitored by TLC. The reactionmixture was diluted with ethylacetate and the organic portion was washedwith water and brine solution, dried over sodium sulphate andconcentrated under reduced pressure to get the crude product which waspurified by column chromatography using ethylacetate-hexane gradient toafford the titled product as sticky oil (LXIV, 1 g, 54%), LC-MS m/zcalcd for C₃₂H₄₃1N₂O₄, 646.2; found 647.1 [M+H]⁺.

Step-2

To a stirred solution of ethyl4-(3-(4-(((tert-butoxycarbonyl)(2-(4-iodophenyl)cyclopropyl)amino)methyl)piperidin-1-yl)propyl)benzoate(LXIV, 1 g, 1.5 mmol) in toluene (50 mL) was addedN,N-dimethylethane-1,2-diamine (0.16 g, 1.80 mmol) and degassed withargon gas for 10 min. Then, palladium acetate (0.008 g, 0.037 mmol),Bis[(2-diphenylphosphino)phenyl] ether (0.080 g, 0.15), chloroform (0.36mL, 4.5 mmol) and cesium hydroxide hydrate (2.51 g, 15.0 mmol) was addedand heated at 100° C. for 24 h. The reaction mixture was cooled to roomtemperature. Then, the reaction mixture was filtered through celite,washed with toluene and concentrated under vacuum. The crude product waspurified by column chromatography using methanol-dichloromethanegradient to afford the titled product as brown colour oil (I-53, 0.57 g,58%), LC-MS m/z calcd for C₃₇H₅₄N₄O₅, 634.4; found 635.4 [M+H]⁺.

I-54 ethyl4-(3-(4-(((tert-butoxycarbonyl)(2-(4-(morpholine-4-carbonyl)phenyl)cyclopropyl)amino)methyl)piperidin-1-yl)propyl)benzoate

The compound I-54 was synthesized following the procedure for thesynthesis of I-53. LC-MS m/z calcd for C₃₇H₅₁N₃O₆, 633.4. found 634.4[M+H]⁺.

I-55 ethyl4-(3-(4-(((tert-butoxycarbonyl)(2-(4-(piperidine-1-carbonyl)phenyl)cyclopropyl)amino)methyl)piperidin-1-yl)propyl)benzoate

The compound was synthesized following the procedure for the synthesisof I-53. LC-MS m/z calcd for C₃₈H₅₃N₃O₅, 631.4. found 632.4 [M+H]⁺.

I-56 methyl4-(3-(4-(((tert-butoxycarbonyl)(2-(4′-chloro-[1,1′-biphenyl]-4-yl)cyclopropyl)amino)methyl)piperidin-1-yl)propyl)benzoate

The compound was synthesized using amine B10 and aldehyde A19 followingthe procedure for the synthesis of I-2. LC-MS m/z calcd forC₃₇H₄₅ClN₂O₄, 616.3. found 617.3 [M+H]⁺.

I-57 ethyl4-(3-(4-(((tert-butoxycarbonyl)(2-(4′-fluoro-[1,1′-biphenyl]-4-yl)cyclopropyl)amino)methyl)piperidin-1-yl)propyl)benzoate

The compound was synthesized using amine B12 and aldehyde A19 followingthe procedure for the synthesis of I-2. LC-MS m/z calcd for C₃₈H₄₇FN₂O₄,614.3. found 615.3 [M+H]⁺.

I-58 methyl4-(3-(3-(((tert-butoxycarbonyl)(2-(4′-fluoro-[1,1′-biphenyl]-4-yl)cyclopropyl)amino)methyl)azetidin-1-yl)propyl)benzoate

The compound was synthesized using amine B22 and methyl4-(3-bromopropyl)benzoate following the procedure for the synthesis ofI-46. LC-MS m/z calcd for C₃₂H₃₂F₄N₂O₃, 568.2. found 569.2 [M+H]⁺.

I-59 ethyl4-(3-(4-(((tert-butoxycarbonyl)(2-(4′-cyano-[1,1′-biphenyl]-4-yl)cyclopropyl)amino)methyl)piperidin-1-yl)propyl)benzoate

The compound was synthesized using amine B13 and aldehyde A19 followingthe procedure for the synthesis of I-2. LC-MS m/z calcd for C₃₉H₄₇N₃O₄,621.3. found 622.3 [M+H]⁺.

I-60 ethyl4-(3-(4-(((tert-butoxycarbonyl)(2-(4-(1-methyl-2-oxo-1,2-dihydropyridin-4-yl)phenyl)cyclopropyl)amino)methyl)piperidin-1-yl)propyl)benzoate

The compound was synthesized using amine B9 and aldehyde A19 followingthe procedure for the synthesis of I-2. LC-MS m/z calcd for C₃₈H₄₉N₃O₅,627.3. found 628.3 [M+H]⁺.

I-61 ethyl4-(3-(4-(((tert-butoxycarbonyl)(2-(4-(pyrimidin-5-yl)phenyl)cyclopropyl)amino)methyl)piperidin-1-yl)propyl)benzoate

The compound was synthesized using amine B11 and aldehyde A19 followingthe procedure for the synthesis of I-2. LC-MS m/z calcd for C₃₆H₄₆N₄O₄,598.3. found 599.3 [M+H]⁺.

I-62 ethyl4-(3-(4-(((tert-butoxycarbonyl)(2-(4-(1-methyl-1H-pyrazol-4-yl)phenyl)cyclopropyl)amino)methyl)piperidin-1-yl)propyl)benzoate

The compound was synthesized using amine B7 and aldehyde A19 followingthe procedure for the synthesis of I-2. LC-MS m/z calcd for C₃₅H₄₆N₄O₄,586.3. found 587.3 [M+H]⁺.

I-63 ethyl4-(3-(3-((2,2,2-trifluoro-N-(2-(4-(1-methyl-1H-pyrazol-4-yl)phenyl)cyclopropyl)acetamido)methyl)azetidin-1-yl)propyl)benzoate-Procedure

The compound was synthesized using amine B23 and ethyl4-(3-bromopropyl)benzoate following the procedure for the synthesis ofI-46. LC-MS m/z calcd for C₃₁H₃₅F₃N₄O₃, 568.2. found 569.2 [M+H]⁺.

I-64 ethyl4-(3-(4-(((tert-butoxycarbonyl)(2-(4-(3,5-dimethylisoxazol-4-yl)phenyl)cyclopropyl)amino)methyl)piperidin-1-yl)propyl)benzoate

The compound was synthesized using amine B8 and aldehyde A19 followingthe procedure for the synthesis of I-2. LC-MS m/z calcd for C₃₇H₄₉N₃O₅,615.4. found 616.4 [M+H]⁺.

I-65 ethyl4-(3-(3-((N-(2-(4-(3,5-dimethylisoxazol-4-yl)phenyl)cyclopropyl)-2,2,2-trifluoroacetamido)methyl)azetidin-1-yl)propyl)benzoate

The compound was synthesized using amine B23 and ethyl4-(3-bromopropyl)benzoate following the procedure for the synthesis ofI-46. LC-MS m/z calcd for C₃₂H₃₆F₃N₃O₄, 583.2 found 584.3 [M+H]⁺.

I-66 ethyl4-(3-(4-(((tert-butoxycarbonyl)(2-(4-(6-(trifluoromethyl)pyridin-3-yl)phenyl)cyclopropyl)amino)methyl)piperidin-1-yl)propyl)benzoate

The compound was synthesized using amine B14 and aldehyde A19 followingthe procedure for the synthesis of I-2. LC-MS m/z calcd forC₃₈H₄₆F₃N₃O₄, 665.3; found 666.3 [M+H]⁺.

I-67 ethyl4-(3-(4-(((tert-butoxycarbonyl)(2-(1-isopropyl-1H-pyrazol-4-yl)cyclopropyl)amino)methyl)piperidin-1-yl)propyl)benzoate

The compound was synthesized using amine B15 and aldehyde A19 followingthe procedure for the synthesis of I-2. LC-MS m/z calcd for C₃₂H₄₈N₄O₄,552.4; found 553.4 [M+H]⁺.

I-68 ethyl4-(3-(4-(((tert-butoxycarbonyl)(2-(1-phenyl-1H-pyrazol-4-yl)cyclopropyl)amino)methyl)piperidin-1-yl)propyl)benzoate

The compound was synthesized using amine B16 and aldehyde A19 followingthe procedure for the synthesis of I-2. LC-MS m/z calcd for C₃₅H₄₆N₄O₄,586.4; found 586.4 [M+H]⁺.

I-69 ethyl4-(3-(4-(((tert-butoxycarbonyl)(2-(2-methylthiazol-5-yl)cyclopropyl)amino)methyl)piperidin-1-yl)propyl)benzoate

The compound was synthesized using amine B17 and aldehyde A19 followingthe procedure for the synthesis of I-2. LC-MS m/z calcd for C₃₀H₄₃N₃O₄S,541.3; found 542.3 [M+H]⁺.

I-70 ethyl4-(3-(4-(((tert-butoxycarbonyl)(2-(pyridin-3-yl)cyclopropyl)amino)methyl)piperidin-1-yl)propyl)benzoate

The compound was synthesized using amine B18 and aldehyde A19 followingthe procedure for the synthesis of I-2. LC-MS m/z calcd for C₃₁H₄₃N₃O₄,521.3; found 522.3 [M+H]⁺.

I-71 ethyl4-(3-(2-(((tert-butoxycarbonyl)(2-(4-methoxyphenyl)cyclopropyl)amino)methyl)-5,6-dihydroimidazo[1,2-a]pyrazin-7(8H)-yl)propyl)benzoate

The compound was synthesized using 4-methoxyphenylcyclopropylamine andaldehyde A18 following the procedure for the synthesis of I-2. LC-MS m/zcalcd for C₃₄H₄₄N₄O₅, 588.3; found 589.3 [M+H]⁺.

I-72 ethyl4-(3-(2-(((tert-butoxycarbonyl)(2-(4-fluorophenyl)cyclopropyl)amino)methyl)-5,6-dihydroimidazo[1,2-a]pyrazin-7(8H)-yl)propyl)benzoate

The compound was synthesized using 4-fluorophenylcyclopropylamine andaldehyde A18 following the procedure for the synthesis of I-2. LC-MS m/zcalcd for C₃₃H₄₁FN₄O₄, 576.3; found 577.3 [M+H]⁺.

I-73 ethyl4-(3-(4-(((tert-butoxycarbonyl)(2-(3,4-difluorophenyl)cyclopropyl)amino)methyl)-1H-imidazol-1-yl)propyl)benzoate

The compound was synthesized using 3,4-difluorophenylcyclopropylamineand aldehyde A8 following the procedure for the synthesis of I-2. LC-MSm/z calcd for C₃₀H₃₅F₂N₃O₄, 539.3; found 540.3 [M+H]⁺.

I-74 ethyl4-(3-(5-(((tert-butoxycarbonyl)(2-phenylcyclopropyl)amino)methyl)-1H-imidazol-1-yl)propyl)benzoate

The compound was synthesized using phenylcyclopropylamine and aldehydeA9 following the procedure for the synthesis of I-2. LC-MS m/z calcd forC₃₀H₃₇N₃O₄, 503.3; found 504.3 [M+H]⁺.

I-75 ethyl4-(3-(4-(((tert-butoxycarbonyl)(2-phenylcyclopropyl)amino)methyl)-1H-imidazol-1-yl)propyl)benzoate

The compound was synthesized using phenylcyclopropylamine and aldehydeA8 following the procedure for the synthesis of I-2. LC-MS m/z calcd forC₃₀H₃₇N₃O₄, 503.4; found 504.3 [M+H]⁺.

I-76 ethyl4-(3-(4-(((2-phenylcyclopropyl)amino)methyl)-1H-pyrazol-1-yl)propyl)benzoate

The compound was synthesized using phenylcyclopropylamine and aldehydeA11 following the procedure for the synthesis of I-2. LC-MS m/z calcdfor C₃₀H₃₇N₃O₄, 503.4 found 504.3 [M+H]⁺.

I-77 ethyl4-(3-(4-(((tert-butoxycarbonyl)(2-phenylcyclopropyl)amino)methyl)-1H-1,2,3-triazol-1-yl)propyl)benzoate

The compound was synthesized using phenylcyclopropylamine and aldehydeA28 following the procedure for the synthesis of I-2. LC-MS m/z calcdfor C₂₉H₃₆N₄O₄, 504.2; found 505.3 [M+H]⁺.

I-78 ethyl4-(3-(6-(((tert-butoxycarbonyl)(2-(4-fluorophenyl)cyclopropyl)amino)methyl)-3,4-dihydroisoquinolin-2(1H)-yl)propyl)benzoate

The compound was synthesized using 4-fluorophenylcyclopropylamine andaldehyde A20 following the procedure for the synthesis of I-2. LC-MS m/zcalcd for C₃₆H₄₃FN₂O₄, 586.3; found 587.3 [M+H]⁺.

I-79 methyl4-((7-(((tert-butoxycarbonyl)(2-(4-fluorophenyl)cyclopropyl)amino)methyl)-3,4-dihydroisoquinolin-2(1H)-yl)methyl)benzoate

The compound was synthesized using phenylcyclopropylamine and aldehydeA22 following the procedure for the synthesis of I-2. LC-MS m/z calcdfor C₃₃H₃₇FN₂O₄, 544.2; found 545.3 [M+H]⁺.

I-80 methyl4-((2-(((tert-butoxycarbonyl)(2-(4-fluorophenyl)cyclopropyl)amino)methyl)-5,6-dihydroimidazo[1,2-a]pyrazin-7(8H)-yl)methyl)benzoate

The compound was synthesized using 4-fluorophenylcyclopropylamine andaldehyde A14 following the procedure for the synthesis of I-2. LC-MS m/zcalcd for C₃₀H₃₅FN₄O₄, 534.2; found 535.3 [M+H]⁺.

I-81 ethyl4-(3-(4-(((tert-butoxycarbonyl)(2-(1,3,3-trimethyl-2-oxoindolin-5-yl)cyclopropyl)amino)methyl)piperidin-1-yl)propyl)benzoate

The compound was synthesized using amine B20 and aldehyde A19 followingthe procedure for the synthesis of I-2. LC-MS m/z calcd for C₃₇H₅₁N₃O₅,617.4; found 618.4 [M+H]⁺.

I-82 methyl4-(3-(4-(((tert-butoxycarbonyl)(2-phenylcyclopropyl)amino)methyl)piperidin-1-yl)-3-oxopropyl)benzoate

The compound was synthesized using phenylcyclopropylamine and aldehydeA29 following the procedure for the synthesis of I-2. LC-MS m/z calcdfor C₃₁H₄₀N₂O₅, 520.3; found 465.2 [M-55]⁺.

I-83 methyl4-(3-(4-((tert-butoxycarbonyl)(2-phenylcyclopropyl)amino)piperidin-1-yl)-3-oxopropyl)benzoate

The compound was synthesized using phenylcyclopropylamine and ketone A23following the procedure for the synthesis of I-2. LC-MS m/z calcd forC₃₀H₃₈N₂O₅, 506.3; found 451.2 [M-55]⁺.

I-84 methyl4-(2-(4-(((tert-butoxycarbonyl)(2-phenylcyclopropyl)amino)methyl)piperidin-1-yl)-2-oxoethyl)benzoate

The compound was synthesized using phenylcyclopropylamine and aldehydeA24 following the procedure for the synthesis of I-2. LC-MS m/z calcdfor C₃₀H₃₈N₂O₅, 506.3; found 451.2 [M-55]⁺.

I-85 methyl4-((4-(((tert-butoxycarbonyl)(2-phenylcyclopropyl)amino)methyl)piperidin-1-yl)sulfonyl)benzoate-

I-854-((4-((2,2,2-trifluoro-N-(2-phenylcyclopropyl)acetamido)methyl)piperidin-1-yl)sulfonyl)benzoic Acid

To a stirred solution of tert-butyl(2-phenylcyclopropyl)(piperidin-4-ylmethyl)carbamate (1 g, 3.03 mmol) indichloromethane (20 mL) was added triethylamine (0.63 mL, 4.5 mmol) andmethyl 4-(chlorosulfonyl)benzoate (0.78 g, 3.33 mmol) at 0° C. andstirred at room temperature for 2 h. The reaction mixture was dilutedwith dichloromethane and washed with 10% aqueous NaHCO₃ solution, water,brine solution, dried over sodium sulphate and concentrated underreduced pressure to afford the titled product as off-white solid (I-85,1.5 g, 92%). LC-MS m/z calcd for C₂₈H₃₆N₂O₆S, 528.2; found 429.1[M-Boc+H]⁺.

I-86 ethyl4-((N-(2-(4-((2,2,2-trifluoro-N-(2-phenylcyclopropyl)acetamido)methyl)piperidin-1-yl)ethyl)sulfamoyl)methyl)benzoate-

The compound was synthesized using amine B-26 and ethyl4-((chlorosulfonyl)methyl)benzoate following the procedure for thesynthesize of I-85. LC-MS m/z calcd for C₂₈H₃₄F₃N₃O₅S, 595.2; found596.3 [M+H]⁺.

I-87 methyl4-(N-(2-(4-((2,2,2-trifluoro-N-(2-(4-fluorophenyl)cyclopropyl)acetamido)methyl)piperidin-1-yl)ethyl)sulfamoyl)benzoate

The compound was synthesized using amine B-25 and methyl4-(chlorosulfonyl)benzoate following the procedure for the synthesize ofI-85. LC-MS m/z calcd for C₂₇H₃₁F₄N₃O₅S, 585.2; found 586.2 [M+H]⁺.

I-88 methyl4-(2-((4-((2,2,2-trifluoro-N-(2-phenylcyclopropyl)acetamido)methyl)piperidin-1-yl)sulfonyl)ethyl)benzoate

The compound was synthesized using2,2,2-trifluoro-N-(2-phenylcyclopropyl)-N-(piperidin-4-ylmethyl)acetamidehydrochloride and methyl 4-(2-(chlorosulfonyl)ethyl)benzoate followingthe procedure for the synthesize of I-85. LC-MS m/z calcd forC₂₇H₃₁F₃N₂O₅S, 552.2; found 553.2 [M+H]⁺.

I-89 methyl4-((2-(4-((2,2,2-trifluoro-N-(2-phenylcyclopropyl)acetamido)methyl)piperidin-1-yl)ethyl)carbamoyl)benzoate

The compound was synthesized using amine B-26 and methyl4-(chlorocarbonyl)benzoate following the procedure for the synthesize ofI-85. LC-MS m/z calcd for C₂₈H₃₂F₃N₃O₄, 531.2; found 532.2 [M+H]⁺.

I-90 methyl4-((2-(4-((N-(2-(3,4-difluorophenyl)cyclopropyl)-2,2,2-trifluoroacetamido)methyl)piperidin-1-yl)ethyl)carbamoyl)benzoate

The compound was synthesized using amine B-27 and methyl4-(chlorocarbonyl)benzoate following the procedure for the synthesize ofI-85. LC-MS m/z calcd for C₂₈H₃₀F₅N₃O₄, 567.2; found 568.2 [M+H]⁺.

I-91 methyl4-((4-(N-(tert-butoxycarbonyl)-N-(2-phenylcyclopropyl)glycyl)piperazin-1-yl)methyl)benzoate

Step-1: tert-butyl4-(4-(methoxycarbonyl)benzyl)piperazine-1-carboxylate-LXVII

To a solution of tert-butyl piperazine-1-carboxylate (LXV, 2 g, 10.8mmol) in acetonitrile (100 mL) was added potassium carbonate (1.7 g,12.9 mmol) and methyl 4-(bromomethyl)benzoate (LXVI, 2.4 g, 10.8 mmol)and stirred for 24 h at room temperature. After completion of reaction,the reaction was concentrated under vacuum and then diluted withethylacetate (50 mL). The organic layer was washed with water, brine,dried over sodium sulfate and concentrated under vacuum to get crudeproduct which was purified by flash column chromatography usingethylacetate-hexane gradient to afford the titled product as colourlessliquid (LXVII, 2.7 g, 75%). LC-MS m/z calcd for C₁₈H₂₆N₂O₄, 334.2; found335.2 [M+H]⁺.

Step-2: methyl 4-(piperazin-1-ylmethyl)benzoate hydrochloride-LXVIII

To a stirred solution of tert-butyl4-(4-(methoxycarbonyl)benzyl)piperazine-1-carboxylate (LXVII, 2.7 g,8.08 mmol) in 1,4-dioxane (50 mL) was added 20% HCl in 1,4-dioxane (50mL) and was stirred for 16 h. The reaction mixture was concentratedunder vacuum. The resultant solid was triturated with diethyl ether. Thesolid was filtered out and dried under vacuum to get the titled productas white solid (LXVIII, 1.8 g, 75%). LC-MS m/z calcd for C₁₃H₁₈N₂O₂,234.2; found 235.2 [M+H]⁺.

Step-3: methyl4-((4-((2-phenylcyclopropyl)glycyl)piperazin-1-yl)methyl)benzoate-I-91

To a stirred solution ofN-(tert-butoxycarbonyl)-N-(2-phenylcyclopropyl)glycine (LXVIII, 0.10 g,0.34 mmol) in dry dichloromethane (10 mL) was added methyl4-(piperazin-1-ylmethyl)benzoate hydrochloride (0.11 g, 0.37 mmol), thentriethylamine (0.24 mL, 1.71 mmol) and cooled to 0° C. T3P (0.6 mL, 0.86mmol) was added and stirred at room temperature for 16 h. Aftercompletion of the reaction, the mixture was quenched with ice-water andextracted with dichloromethane (10 mL×3). The organic layer was washedwith water, brine, dried over sodium sulphate and concentrated underreduced pressure to afford the crude product which was purified bycolumn chromatography using methanol-dichloromethane to afford thetitled product as gummy solid (I-91, 0.1 g, 57%). LC-MS m/z calcd forC₂₉H₃₇N₃O₅, 507.3; found 508.3 [M+H]⁺.

I-92 methyl4-((4-(2-((tert-butoxycarbonyl)(2-phenylcyclopropyl)amino)acetyl)piperazin-1-yl)methyl)benzoate

Step 1: Methyl 4-(3-oxo-3-(piperazin-1-yl)propyl)benzoate-LXIX

To a stirred solution of 3-(4-(methoxycarbonyl)phenyl)propanoic acid(0.29 g, 1.41 mmol) and piperazine (0.36 g, 4.25 mmol), indichloromethane (15 mL) was added triethylamine (0.60 g, 4.25 mmol), thereaction was stirred at room temperature for 10 min, then cooled to 0°C. and added propylphosphonic anhydride (1.04 mL, 3.54 mmol), and theresulting mixture was stirred at room temperature for 3 h. The reactionwas monitored by TLC, after completion of reaction, the mixture wasquenched with ice. The reaction mixture was diluted with water andextracted with dichloromethane (3×25 mL). The organic portion was washedwith water and brine, dried over sodium sulphate and concentrated underreduced pressure to get the crude light pale yellow oil (LXIX, 0.37 g,93%). LC-MS m/z calcd for C₁₅H₂₀N₂O₃, 276.2; found 278.3 [M+H]⁺.

Step 2: methyl4-(3-(4-(N-(tert-butoxycarbonyl)-N-(2-phenylcyclopropyl)glycyl)piperazin-1-yl)-3-oxopropyl)benzoate-I-92

To a solution of N-(tert-butoxycarbonyl)-N-(2-phenylcyclopropyl)glycine(LXIX, 0.2 g, 0.69 mmol) in dichloromethane (15 mL) was added methyl4-(3-oxo-3-(piperazin-1-yl)propyl)benzoate (0.23 g, 0.82 mmol), triethylamine (0.29 mL, 2.05 mmol) to 0° C. and then T₃P was added (0.50 mL,1.72 mmol). The resulting mixture was stirred at room temperature for 3h. After completion of reaction, the mixture was diluted withdichloromethane (20 mL). The combined organic layer was washed withwater, brine solution, dried over sodium sulphate and concentrated underreduced pressure to afford the title product as stick oil (0.37 g,quantitative yield). LC-MS m/z calcd for C₃₁H₃₉N₃O₆, 549.3; found 550.3[M+H]⁺.

I-93 methyl4-(3-(1-(2-((tert-butoxycarbonyl)(2-phenylcyclopropyl)amino)acetyl)piperidin-4-yl)propyl)benzoate

Step 1: tert-butyl 4-(2-hydroxyethyl)piperidine-1-carboxylate (LXXI)

To a stirred solution of 2-(piperidin-4-yl)ethanol (LXX, 1 g, 7.72 mmol)in tetrahydrofuran and water mixture (40 mL, 1:1) was added sodiumbicarbonate (1.62 g, 19.32 mmol) and Boc anhydride (2.6 mL, 11.6 mmol)at room temperature and stirred for 3 h. The reaction mixture wasdiluted with ethyl acetate and the organic portion was washed with waterand brine, dried over sodium sulphate and concentrated under reducedpressure to get the crude product which was purified by flash columnchromatography using ethylacetate-hexane gradient to afford the titledproduct as gummy solid (LXXI, 1.6 g, 88%). LC-MS m/z calcd forC₁₂H₂₃NO₃, 229.2; found 130.2 [M-Boc]⁺.

Step 2: tert-butyl 4-(2-oxoethyl)piperidine-1-carboxylate (LXXII)

To a stirred solution of tert-butyl4-(2-hydroxyethyl)piperidine-1-carboxylate (LXXI, 1.5 g, 6.55 mmol) indry dichloromethane (40 mL) was added Dess-Martin periodinane (3.3 g,7.86 mmol) at 0° C. and the resulting mixture was stirred at roomtemperature for 5 h. The reaction mixture was quenched with 10% sodiumthiosulphate solution (20 mL) and saturated sodium bicarbonate solution(20 mL) and then extracted with dichloromethane (2×50 mL). The organicportion was washed with saturated sodium bicarbonate solution, water,brine, dried over sodium sulphate and concentrated under reducedpressure to afford the product as yellow semi-solid (LXXII, 0.9 g, 60%).

Step 3: (E)-tert-butyl4-(3-(4-(methoxycarbonyl)phenyl)allyl)piperidine-1-carboxylate (LXXIII)

To a stirred solution of methyl 4-((diethoxyphosphoryl)methyl)benzoate(0.9 g, 3.96 mmol) in dry THF (40 mL) was added 60% sodium hydride at 0°C. and stirred for 1 h. Solution of tert-butyl4-(2-oxoethyl)piperidine-1-carboxylate (LXXII, 1.1 g, 3.96 mmol) in dryTHF was added and stirred further 2 h at room temperature. The reactionmixture was quenched with saturated ammonium chloride and then extractedwith ethyl acetate (100 mL). The organic portion was washed with water,brine, dried over sodium sulphate and concentrated under reducedpressure to get the crude product which was purified by columnchromatography using ethylacetate-hexane gradient to afford the titledproduct as colourless liquid (LXXIII, 0.7 g, 50%). LC-MS m/z calcd forC₂₁H₂₉NO₄, 359.2; found 260.2 [M-Boc+H]⁺.

Step 4: Tert-butyl4-(3-(4-(methoxycarbonyl)phenyl)propyl)piperidine-1-carboxylate (LXXIV)

To a stirred solution of (E)-tert-butyl4-(3-(4-(methoxycarbonyl)phenyl)allyl)piperidine-1-carboxylate (LXXIII,0.71 g, 1.97 mmol) in methanol (20 mL) was added 10% Pd—C and stirredfor 0.5 h in hydrogen balloon at room temperature. The reaction mixturewas filtered out through celite and washed with methanol. The filtratewas concentrated under vacuum to afford the title product as colourlesssticky solid (LXXIV, 0.71 g, 99%). LC-MS m/z calcd for C₂₁H₃₁NO₄, 361.2;found 262.2 [M-Boc+H]⁺.

Step 5: Methyl 4-(3-(piperidin-4-yl)propyl)benzoatehydrochloride-Intermediate LXXV

To a stirred solution of tert-butyl4-(3-(4-(methoxycarbonyl)phenyl)propyl)piperidine-1-carboxylate (LXXIV,0.7 g, 1.9 mmol) in dioxane (15 mL) was added 20% HCl in dioxane at 0°C. and stirred for 16 h at room temperature. The reaction mixture wasconcentrated under vacuum to afford the title product as off-white solid(LXXV, 0.41 g, 72%). LC-MS m/z calcd for C₁₆H₂₃NO₂, 261.1; found 262.2[M+H]⁺.

Step 6: Methyl4-(3-(1-(N-(tert-butoxycarbonyl)-N-(2-phenylcyclopropyl)glycyl)piperidin-4-yl)propyl)benzoate-I-93

To a stirred solution ofN-(tert-butoxycarbonyl)-N-(2-phenylcyclopropyl)glycine (0.1 g, 0.34mmol) and methyl 4-(3-(piperidin-4-yl)propyl)benzoate hydrochloride(LXXV, 0.11 g, 0.37 mmol) in DMF (2 mL) was added EDC.HCl (0.058 g, 0.37mmol), HOBt (0.05 g, 0.37 mmol) and DIPEA (0.13 mL, 1.03 mmol) at 0° C.and the resulting mixture was stirred at room temperature for 16 h. Thereaction mixture was diluted with water and extracted with ethylacetate. Organic portion was washed with water and brine, dried oversodium sulphate and concentrated under reduced pressure to get the crudeproduct which was purified by column chromatography usingethylacetate-hexane gradient to afford the titled product as an stickyoil (I-93, 0.12 g, 68%). LC-MS m/z calcd for C₃₂H₄₂N₂O₅, 534; found 535[M+H]⁺.

I-94 ethyl4-(3-(4-(((tert-butoxycarbonyl)(2-phenylcyclopropyl)amino)methyl)-2-oxopiperidin-1-yl)propyl)benzoate

The compound was synthesized using phenylcyclopropylamine and aldehydeA17 following the procedure for the synthesis of I-2. LC-MS m/z calcdfor C₃₂H₄₂N₂O₅, 534.3; found 535.2 [M+H]⁺.

I-95 methyl4-(2-((tert-butoxycarbonyl)(2-phenylcyclopropyl)amino)ethoxy)benzoate

Step 1: Methyl 4-(2-((2-phenylcyclopropyl)amino)ethoxy)benzoate (LXXVII)

To a stirred solution of methyl 4-(2-bromoethoxy)benzoate (LXXVI, 0.45g, 1.77 mmol) in dimethylformamide (15 mL) was added2-phenylcyclopropanamine (0.5 g, 2.95 mmol) and potassium carbonate(1.22 g, 8.84 mmol) and the resulting mixture was stirred at 60° C.temperature for 12 h. Reaction was monitored by TLC, after completion ofreaction, reaction was quenched with ice and the solvent was completelyremoved to get the residue. Water was added and the residue wasextracted with dichloromethane (3×25 mL). The organic portion was washedwith water and brine, dried over sodium sulphate and concentrated underreduced pressure to get the crude product which was purified bycombi-flash chromatography using ethylacetate-hexane gradient to affordthe required product as white solid (LXXVII, 0.32 g, 35%), LC-MS m/zcalcd for C₁₉H₂₁NO₃, 311.1; found 312.2 [M+H]⁺.

Step 2: Methyl4-(2-((tert-butoxycarbonyl)(2-phenylcyclopropyl)amino)ethoxy)benzoate(I-95)

To a stirred solution of methyl4-(2-((2-phenylcyclopropyl)amino)ethoxy)benzoate (LXXVII, 0.2 g, 0.64mmol) in tetrahydrofuran and water mixture (14 mL, 1:1) was added sodiumbicarbonate (0.16 g, 1.92 mmol) and Boc anhydride (0.16 mL, 0.77 mmol)at room temperature and the resulting mixture was stirred at thattemperature for 1 h. The progress of the reaction was monitored by TLC.The reaction mixture was diluted with ethylacetate and the organicportion was washed with water and brine, dried over sodium sulphate andconcentrated under reduced pressure to get the crude product which waspurified by column chromatography using ethylacetate-hexane gradient toafford the titled product as pale-yellow oil (I-95, 0.16 g, 61%). LC-MSm/z calcd for C₂₄H₂₉NO₅, 411.2; found 312.1 [M-Boc+H]⁺.

I-96 methyl6-(2-(4-((2,2,2-trifluoro-N-(2-(4-fluorophenyl)cyclopropyl)acetamido)methyl)piperidin-1-yl)ethoxy)nicotinate

Step 1: methyl 6-(2-bromoethoxy)nicotinate

To a solution of methyl 6-hydroxynicotinate (1.2 g, 7.84 mmol) in DMF(10 mL) was added 60% of sodium hydride (0.75 g, 17.25 mmol) at 0° C.Then 1,2-dibromoethane (6.57 mL, 7.84 mmol) was added and then stirredfor 16 h at room temperature. After completion of reaction, the reactionwas quenched with ice and extracted with ethylacetate (2×50 mL). Thecombined organic layer was washed with water, brine solution, dried oversodium sulfate and concentrated under vacuum to get crude product whichwas purified by column chromatography using ethylacetate-hexane gradientto afford the titled product as a white solid (LXXVIII, 0.73 g, 35%).LC-MS m/z calcd for C₉H₁₀BrNO₃, 259.0; found 261.0 [M+H]⁺.

Step 2: methyl6-(2-(4-((2,2,2-trifluoro-N-(2-(4-fluorophenyl)cyclopropyl)acetamido)methyl)piperidin-1-yl)ethoxy)nicotinate-I-96

To a solution of methyl 6-(2-bromoethoxy)nicotinate (LXXVIII, 0.54 g, 2mmol) in acetonitrile (5 mL) was added2,2,2-trifluoro-N-(2-(4-fluorophenyl)cyclopropyl)-N-(piperidin-4-ylmethyl)acetamidehydrochloride (B-3, 0.80 g, 2 mmol) and N,N-diisopropylethylamine (1.07mL, 6 mmol). Then the reaction mixture was heated at 40° C. for 16 h.After completion of reaction, the reaction was diluted with ethylacetate (50 mL), washed with water, brine, dried over sodium sulfate andconcentrated under vacuum to get crude product which was purified bycolumn chromatography using methanol-dichloromethane gradient to affordthe titled product as a brown colour liquid (I-96, 0.8 g, 74%). LC-MSm/z calcd for C₂₆H₂₉F₄N₃O₄, 523; found 524 [M+H]⁺.

I-97 methyl6-(2-(4-((2,2,2-trifluoro-N-(2-phenylcyclopropyl)acetamido)methyl)piperidin-1-yl)ethoxy)nicotinate

The compound was synthesized using phenylcyclopropylamine following theprocedure for the synthesis of I-96. LC-MS m/z calcd for C₂₆H₃₀F₃N₃O₄,505.2; found 506.2 [M+H]⁺.

I-98 methyl6-(2-(4-((2,2,2-trifluoro-N-(2-(4′-fluoro-[1,1′-biphenyl]-4-yl)cyclopropyl)acetamido)methyl)piperidin-1-yl)ethoxy)nicotinate

The compound was synthesized using amine B-12 following the procedurefor the synthesis of I-96. LC-MS m/z calcd for C₃₂H₃₃F₄N₃O₄, 599.2;found 600.2 [M+H]⁺.

I-99 methyl4-(2-(4-((2,2,2-trifluoro-N-(2-phenylcyclopropyl)acetamido)methyl)piperidin-1-yl)ethoxy)benzoate

The compound was synthesized using phenylcyclopropylamine following theprocedure for the synthesis of I-95. LC-MS m/z calcd for C₂₇H₃₁F₃N₂O₄,504.2; found 505.2 [M+H]⁺.

I-100 methyl4-(3-(4-((2,2,2-trifluoro-N-(2-phenylcyclopropyl)acetamido)methyl)piperidin-1-yl)propoxy)benzoate

The compound was synthesized using phenylcyclopropylamine following theprocedure for the synthesis of I-95. LC-MS m/z calcd for C₂₈H₃₃F₃N₂O₄,518.2; found 519.2 [M+H]⁺.

I-101 methyl4-(3-((tert-butoxycarbonyl)(2-phenylcyclopropyl)amino)propoxy)benzoate

The compound was synthesized using phenylcyclopropylamine following theprocedure for the synthesis of I-95. LC-MS m/z calcd for C₂₅H₃₁NO₅,425.2; found 426.1 [M+H]⁺.

I-102 methyl2-((2-(4-((2,2,2-trifluoro-N-(2-(4-fluorophenyl)cyclopropyl)acetamido)methyl)piperidin-1-yl)ethyl)amino)pyrimidine-5-carboxylate

To a solution ofN-((1-(2-aminoethyl)piperidin-4-yl)methyl)-2,2,2-trifluoro-N-(2-(4-fluorophenyl)cyclopropyl)acetamidehydrochloride. (B-25, 0.48 g, 1.60 mmol) in acetonitrile (5 mL) wasadded methyl 2-(ethylsulfonyl)pyrimidine-5-carboxylate (0.4 g, 1.7 mmol)and N,N-diisopropylethylamine (0.86 mL, 4.8 mmol). Then the reactionmixture was heated at 50° C. for 16 h. After completion of reaction, thereaction was diluted with ethylacetate (50 mL), washed with water, brinesolution, dried over sodium sulfate and concentrated under vacuum to getcrude product which was purified by column chromatography usingmethanol-dichloromethane gradient to afford the titled product as browncolour sticky oil (I-102, 0.250 g, 41%). LC-MS m/z calcd forC₂₆H₃₁F₄N₅O₃, 537.2; found 538.2 [M+H]⁺.

I-103 ethyl5-(2-((tert-butoxycarbonyl)(2-(4-fluorophenyl)cyclopropyl)amino)acetyl)-4,5,6,7-tetrahydrothieno[3,2-c]pyridine-2-carboxylate

Step 1:5-(tert-butyl)-2-ethyl-6,7-dihydrothieno[3,2-c]pyridine-2,5(4H)-dicarboxylateLXXIX

To a stirred solution of tert-butyl6,7-dihydrothieno[3,2-c]pyridine-5(4H)-carboxylate (11.5 g, 48.09 mmol)in tetrahydrofuran (75 mL) was added 1.6M solution of n-butyl lithium inn-hexane (36 mL, 57.71 mmol) at −78° C. and stirred for same temperaturefor 3 h, ethyl chloroformate (52.19 g, 480.9 mmol) was added drop wiseat −78° C. and allowed to stirred for 12 h at room temperature. Progressof reaction followed by TLC. After completion of reaction, the mixturewas quenched with ammonium chloride (100 mL) and extracted withethylacetate. The organic portion was washed with water and brine driedover sodium sulphate and concentrated under reduced pressure to affordthe crude product which was purified by column chromatography usingethylacetate-hexane gradient to afford LXXIX as yellowish liquid (3.75g, 23%). LC-MS m/z calcd for C₁₅H₂₁NO₄S, 311.1. found 212.1 [M-Boc+H]⁺.

Step 2: ethyl 4,5,6,7-tetrahydrothieno[3,2-c]pyridine-2-carboxylate TFAsalt LXXX

To a stirred solution of5-(tert-butyl)-2-ethyl-6,7-dihydrothieno[3,2-c]pyridine-2,5(4H)-dicarboxylate(LXXIX, 0.5 g, 1.68 mmol) in dichloromethane (15 mL) was addedtrifluoroacetic acid (1.5 g, 13.47 mmol) at 0° C. and allowed to stirredfor 4 h at room temperature. Progress of reaction was followed by TLC.After completion of reaction, the mixture was concentrated completelyand washed with diethyl ether to afford product LXXX as a brown colourliquid (0.50 g, 91%). LC-MS m/z calcd for C₁₀H₁₃NO₂S, 211.0. found 212.1[M+H]⁺.

Step 3: ethyl5-(N-(tert-butoxycarbonyl)-N-(2-(4-fluorophenyl)cyclopropyl)glycyl)-4,5,6,7-tetrahydrothieno[3,2-c]pyridine-2-carboxylateI-103

To a stirred solution of ethyl 4,5,6,7-tetrahydrothieno[3,2-c]pyridine-2-carboxylate TFA salt 4 (0.2 g, 0.65 mmol),N-(tert-butoxycarbonyl)-N-(2-(4-fluorophenyl)cyclopropyl)glycine 5 (0.16g, 0.78 mmol), triethylamine (0.261 g, 2.59 mmol) in dichloromethane (10mL) was added propylphosphonic anhydride (T3P, 0.514 g, 1.62 mmol) andstirred for 12 h at room temperature. Progress of reaction followed byTLC. After completion, the reaction was quenched with water (20 mL) andextracted with dichloromethane (2×30 mL). The organic portion was washedwith water, brine, dried over sodium sulphate and concentrated underreduced pressure to afford the crude product which was purified bycolumn chromatography chromatography using ethylacetate-hexane gradientto afford the titled product I-103 as colourless liquid (0.15 g, 57%).LC-MS m/z calcd for C₂₆H₃₁FN₂O₅S, 502.2. found 503.2 [M+H]⁺.

I-104 methyl2-(2-((tert-butoxycarbonyl)(2-(4-fluorophenyl)cyclopropyl)amino)acetyl)-1,2,3,4-tetrahydroisoquinoline-7-carboxylate

To a stirred solution of methyl1,2,3,4-tetrahydroisoquinoline-7-carboxylate hydrochloride (0.25 g, 1.1mmol) and2-((tert-butoxycarbonyl)(2-(4-fluorophenyl)cyclopropyl)amino)acetic acid(0.34 g, 1.1 mmol) in N,N-dimethylformamide (5 mL), was added EDC.HCl(0.42 g, 2.2 mmol), HOBt (0.18 g, 1.32 mmol) and triethylamine (0.61 mL,4.4 mmol) at room temperature. The resulting mixture was stirred at thattemperature for 16 h. The progress of the reaction was monitored by TLC.After completion, the reaction mixture was diluted with water andextracted with ethylacetate. Organic portion was washed with water andbrine, dried over sodium sulphate and concentrated under reducedpressure to get the crude product which was purified by columnchromatography using ethylacetate-hexane gradient to afford the titledproduct as an off-white solid (I-104, 0.25 g, 47%). LC-MS m/z calcd forC₂₇H₃₁FN₂O₅, 482.2; found 483.1 [M+H]⁺.

I-105 ethyl5-(4-((tert-butoxycarbonyl)(2-(4-fluorophenyl)cyclopropyl)amino)butanoyl)-4,5,6,7-tetrahydrothieno[3,2-c]pyridine-2-carboxylate

The compound was synthesized using 2-(4-fluorophenyl)cyclopropanamineand A-25 following the procedure for the synthesis of I-2. LC-MS m/zcalcd for C₂₈H₃₅FN₂O₅S, 530.2; found 531.2 [M+H]⁺.

I-106 ethyl5-(4-(4-((2,2,2-trifluoro-N-(2-(4-fluorophenyl)cyclopropyl)acetamido)methyl)piperidin-1-yl)butanoyl)-4,5,6,7-tetrahydrothieno[3,2-c]pyridine-2-carboxylate

The compound was synthesized using amine B-3 and A25 following theprocedure for the synthesis of I-2. LC-MS m/z calcd for C₃₁H₃₇F₄N₃O₄S,623.2; found 624.3 [M+H]⁺.

I-107 ethyl2-(4-((tert-butoxycarbonyl)(2-(4-fluorophenyl)cyclopropyl)amino)butanoyl)-1,2,3,4-tetrahydroisoquinoline-7-carboxylate

The compound was synthesized using 2-(4-fluorophenyl)cyclopropanamineand A-26 following the procedure for the synthesis of I-2. LC-MS m/zcalcd for C₂₉H₃₅FN₂O₅, 510.2; found 511.3 [M+H]⁺.

I-108 methyl2-(4-((tert-butoxycarbonyl)(2-(4-fluorophenyl)cyclopropyl)amino)butanoyl)isoindoline-5-carboxylate

The compound was synthesized using 2-(4-fluorophenyl)cyclopropanamineand A-27 following the procedure for the synthesis of I-2. LC-MS m/zcalcd for C₂₈H₃₃FN₂O₅, 496.2; found 497.2 [M+H]⁺.

I-109 methyl2-(4-(4-((2,2,2-trifluoro-N-(2-phenylcyclopropyl)acetamido)methyl)piperidin-1-yl)butanoyl)isoindoline-5-carboxylate

The compound was synthesized using2,2,2-trifluoro-N-(2-phenylcyclopropyl)-N-(piperidin-4-ylmethyl)acetamideand ketone A27 following the procedure for the synthesis of I-2. LC-MSm/z calcd for C₃₁H₃₆F₃N₃O₄, 571.2; found 572.3 [M+H]⁺.

I-110 methyl2-(3-(4-((2,2,2-trifluoro-N-(2-phenylcyclopropyl)acetamido)methyl)piperidin-1-yl)propyl)thiazole-4-carboxylate

The compound was synthesized using2,2,2-trifluoro-N-(2-phenylcyclopropyl)-N-(piperidin-4-ylmethyl)acetamideand aldehyde A30 following the procedure for the synthesis of I-2. LC-MSm/z calcd for C₂₅H₃₀F₃N₃O₃S, 509.2; found 510.2 [M+H]⁺.

I-111 methyl2-(3-(4-((2,2,2-trifluoro-N-(2-(4′-fluoro-[1,1′-biphenyl]-4-yl)cyclopropyl)acetamido)methyl)piperidin-1-yl)propyl)thiazole-4-carboxylate

The compound was synthesized using2,2,2-trifluoro-N-(2-phenylcyclopropyl)-N-(piperidin-4-ylmethyl)acetamideand aldehyde A30 following the procedure for the synthesis of I-2. LC-MSm/z calcd for C₃₁H₃₃F₄N₃O₃S, 603.2; found 604.2 [M+H]⁺.

I-112 ethyl2-(3-(4-((2,2,2-trifluoro-N-(2-phenylcyclopropyl)acetamido)methyl)piperidin-1-yl)propyl)thiazole-5-carboxylate

The compound was synthesized using amine2,2,2-trifluoro-N-(2-phenylcyclopropyl)-N-(piperidin-4-ylmethyl)acetamideand aldehyde A31 following the procedure for the synthesis of I-2. LC-MSm/z calcd for C₂₆H₃₂F₃N₃O₃S, 523.2; found 524.2 [M+H]⁺.

I-113 methyl2-(3-(4-((2,2,2-trifluoro-N-(2-phenylcyclopropyl)acetamido)methyl)piperidin-1-yl)propyl)oxazole-4-carboxylate

The compound was synthesized using amine2,2,2-trifluoro-N-(2-phenylcyclopropyl)-N-(piperidin-4-ylmethyl)acetamideand aldehyde A32 following the procedure for the synthesis of I-2. LC-MSm/z calcd for C₂₅H₃₀F₃N₃O₄, 493.2; found 494.2 [M+H]⁺.

I-114 (E)-methyl4-(3-(4-(((tert-butoxycarbonyl)(2-phenylcyclopropyl)amino)methyl)piperidin-1-yl)-3-oxoprop-1-en-1-yl)benzoate

The compound was synthesized using 2-phenylcyclopropanaminehydrochloride and aldehyde A33 following the procedure for the synthesisof I-2. LC-MS m/z calcd for C₃₁H₃₈N₂O₅, 518.2; found 519.3 [M+H]⁺.

I-115 Methyl4-((E)-3-(4-(((tert-butoxycarbonyl)((1S,2R)-2-(4-fluorophenyl)cyclopropyl)amino)methyl)piperidin-1-yl)-3-oxoprop-1-en-1-yl)benzoate

The compound was synthesized using B1 and aldehyde A33 following theprocedure for the synthesis of I-2. LC-MS m/z calcd for C₃₁H₃₇FN₂O₅,536.2; found 537.2 [M+H]⁺.

I-116(E)-methyl4-(3-(4-(((tert-butoxycarbonyl)(2-(4-(3,5-dimethylisoxazol-4-yl)phenyl)cyclopropyl)amino)methyl)piperidin-1-yl)-3-oxoprop-1-en-1-yl)benzoate

The compound was synthesized using B8 and aldehyde A33 following theprocedure for the synthesis of I-2. LC-MS m/z calcd for C₃₆H₄₃N₃O₆,613.3; found 614.2 [M+H]⁺.

I-117(E)-methyl4-(3-(4-(((tert-butoxycarbonyl)(2-(4-(pyrimidin-5-yl)phenyl)cyclopropyl)amino)methyl)piperidin-1-yl)-3-oxoprop-1-en-1-yl)benzoate

The compound was synthesized using B11 and aldehyde A33 following theprocedure for the synthesis of I-2. LC-MS m/z calcd for C₃₅H₄₀N₄O₅,596.3; found 597.3 [M+H]⁺.

I-118(E)-methyl4-(3-oxo-3-(3-((2,2,2-trifluoro-N-(2-(4-fluorophenyl)cyclopropyl)acetamido)methyl)azetidin-1-yl)prop-1-en-1-yl)benzoate

To a stirred solution of methyl(E)-4-(3-oxo-3-(3-((2,2,2-trifluoro-N-(2-(4-fluorophenyl)cyclopropyl)acetamido)methyl)azetidin-1-yl)prop-1-en-1-yl)benzoateTFA salt (B-4, 0.50 g, 1.51 mmol) and(E)-3-(4-(methoxycarbonyl)phenyl)acrylic acid (0.40 g, 1.97 mmol) indichloromethane (20 mL), was added HOBt (0.05 g, 0.30 mmol) andtriethylamine (0.46 mL, 4.55 mmol) at room temperature and cooled to 0°C. Then, EDC.HCl (0.43 g, 2.27 mmol) was added and stirred for 16 h atroom temperature. The reaction mixture was diluted with water andextracted with dichloromethane. The combined organic portion was washedwith water, brine, dried over sodium sulphate and concentrated underreduced pressure to get the crude product which was purified by columnchromatography using methanol-dichloromethane gradient to afford thetitled product as a off-white solid (B-118, 0.49 g, 65%). LC-MS m/zcalcd for C₂₆H₂₄F₄N₂O₄, 504.2; found 505.2 [M+H]⁺.

I-119(E)-methyl4-(3-oxo-3-(3-((2,2,2-trifluoro-N-(2-(4-(1-methyl-1H-pyrazol-4-yl)phenyl)cyclopropyl)acetamido)methyl)azetidin-1-yl)prop-1-en-1-yl)benzoate

Step-1: methyl(E)-4-(3-(3-(((tert-butoxycarbonyl)(2-(4-iodophenyl)cyclopropyl)amino)methyl)azetidin-1-yl)-3-oxoprop-1-en-1-yl)benzoate-LXXXII

To a stirred solution of methyl(E)-4-(3-oxo-3-(3-((2,2,2-trifluoro-N-(2-(4-iodophenyl)cyclopropyl)acetamido)methyl)azetidin-1-yl)prop-1-en-1-yl)benzoate(LXXXI, 0.2 g, 0.33 mmol) in methanol (5 mL) was added potassiumcarbonate (0.1 g, 2.40 mmol) at room temperature and the resultingmixture was stirred at that temperature for 3 h. After completion of thereaction, solvent was evaporated under vacuum. The residue was mixedwith tetrahydrofuran-water mixture (6 mL, 1:1). This was followed byaddition of Boc anhydride (0.08 mL, 0.39 mmol) and sodium bicarbonate(0.08 g, 0.98 mmol). The reaction mixture was stirred for 2 h at roomtemperature. The solvent was evaporated and then diluted withdichloromethane. The combined portion was washed with water and brinesolution, dried over sodium sulphate and concentrated under reducedpressure to get the crude to afford the titled product as stick oil(LXXXII, 0.25 g, 63%). LC-MS m/z calcd for C₂₉H₃₃1N₂O₅, 616.1; found617.1 [M+H]⁺.

Step-2: Methyl(E)-4-(3-(3-(((tert-butoxycarbonyl)(2-(4-(1-methyl-1H-pyrazol-4-yl)phenyl)cyclopropyl)amino)methyl)azetidin-1-yl)-3-oxoprop-1-en-1-yl)benzoate-I-119

To a stirred solution of methyl(E)-4-(3-(3-(((tert-butoxycarbonyl)(2-(4-iodophenyl)cyclopropyl)amino)methyl)azetidin-1-yl)-3-oxoprop-1-en-1-yl)benzoate(LXXXII, 0.25 g, 0.41 mmol) in DMF (3 mL) was added(1-methyl-1H-pyrazol-4-yl)boronic acid (0.06 g, 0.49 mmol) and potassiumcarbonate (0.11 g, 0.82 mmol) and then degassed for 5 min.1,1′-Bis(diphenylphosphino)ferrocene-palladium(II)dichloridedichloromethane complex (0.016 g, 0.02 mmol) was added and heated at120° C. in microwave for 2 h. Water was added and the residue wasextracted with ethylacetate (2×100 mL). The organic portion was washedwith water, brine, dried over sodium sulphate and concentrated underreduced pressure to afford the crude product which was purified bycolumn chromatography using methanol-dichloromethane gradient to affordthe titled product as sticky oil (I-119, 0.2 g, 86%). LC-MS m/z calcdfor C₃₃H₃₈N₄O₅, 570.3; found 571.2 [M+H]⁺.

Synthesis of Acid Intermediates I-120(E)-3-(4-(((tert-butoxycarbonyl)(2-(4-fluorophenyl)cyclopropyl)amino)methyl)phenyl)acrylicAcid

To a stirred solution of (E)-methyl3-(4-(((tetra-butoxycarbonyl)(2-(4-florophenyl)cyclopropl)amino)methyl)phenyl)acrylate(I-2, 0.38 g, 0.89 mmol) in methanol and water mixture (20 mL, 4:1) wasadded sodium hydroxide (0.11 g, 2.68 mmol) at room temperature and theresulting mixture was stirred at that temperature for 1 h. The progressof the reaction was monitored by TLC. After completion of reaction,solvent was evaporated and washed with ethylacetate. The reactionmixture was acidified to pH 5 with 2N HCl and extracted withdichloromethane and the organic portion was washed with water, brinesolution, dried over sodium sulphate and concentrated under reducedpressure to afford the product as off-white solid (I-120, 0.31 g, 86%).LC-MS m/z calcd for C₂₄H₂₆FNO₄, 411.2; found 312.2 [M-Boc+H]⁺.

I-1214-(3-(4-(((tert-butoxycarbonyl)(2-phenylcyclopropyl)amino)methyl)piperidin-1-yl)propyl)benzoicAcid

The compound was synthesized using I-43 following the procedure for thesynthesis of I-120. LC-MS m/z calcd for C₃₀H₄₀N₂O₄, 492.3; found 493.3[M+H]⁺.

I-1224-(3-(4-(((tert-butoxycarbonyl)(2-(4-fluorophenyl)cyclopropyl)amino)methyl)piperidin-1-yl)propyl)benzoicAcid

The compound was synthesized using I-47 following the procedure for thesynthesis of I-120. LC-MS m/z calcd for C₃₀H₃₉FN₂O₄, 510.3; found 511.3[M+H]⁺.

I-1234-(3-(4-(((tert-butoxycarbonyl)(2-(4-methoxyphenyl)cyclopropyl)amino)methyl)piperidin-1-yl)propyl)benzoicAcid

The compound was synthesized using I-51 following the procedure for thesynthesis of I-120. LC-MS m/z calcd for C₃₁H₄₂N₂O₅, 522.3; found 523.3[M+H]⁺.

I-1244-(3-(4-(((tert-butoxycarbonyl)(2-(3,4-difluorophenyl)cyclopropyl)amino)methyl)piperidin-1-yl)propyl)benzoicAcid

The compound was synthesized using I-50 following the procedure for thesynthesis of intermediate I-120. LC-MS m/z calcd for C₃₀H₃₈F₂N₂O₄,528.3; found 529.3 [M+H]⁺.

I-1254-(3-(4-(((tert-butoxycarbonyl)(2-(4-(piperidine-1-carbonyl)phenyl)cyclopropyl)amino)methyl)piperidin-1-yl)propyl)benzoicAcid

The compound was synthesized using I-54 following the procedure for thesynthesis of intermediate I-120. LC-MS m/z calcd for C₃₆H₄₉N₃O₅, 603.4;found 604.4 [M+H]⁺.

I-1274-(3-(6-((tert-butoxycarbonyl)(2-phenylcyclopropyl)amino)-2-azaspiro[3.3]heptan-2-yl)propyl)benzoicAcid

Step:4-(3-(6-((tert-butoxycarbonyl)(2-phenylcyclopropyl)amino)-2-azaspiro[3.3]heptan-2-yl)propyl)benzoicAcid

To a stirred solution of ethyl4-(3-(6-(2,2,2-trifluoro-N-(2-phenylcyclopropyl)acetamido)-2-azaspiro[3.3]heptan-2-yl)propyl)benzoate(0.4 g, 0.77 mmol) in tetrahydrofuran and water mixture (10 mL, 1:1) wasadded lithium hydroxide (0.097 g, 2.30 mmol) at room temperature and theresulting mixture was stirred at that temperature for 3 h. Afterdisappearance of starting material 1-46, Boc anhydride (0.33 mL, 1.50mmol) was added and stirred for 2 h at room temperature. The reactionsolvent was evaporated and then acidified with 2N HCl solution. Theaqueous layer was extracted with dichloromethane (50 mL×2). The combinedorganic layer was washed with water, brine solution, dried over sodiumsulphate and concentrated under reduced pressure to afford the titledproduct as brown solid (0.31 g, 81%). LC-MS m/z calcd for C₃₀H₃₈N₂O₄,490.3; found 489.3 [M−H]⁺.

I-1284-(3-(4-(((tert-butoxycarbonyl)(2-(1-isopropyl-1H-pyrazol-4-yl)cyclopropyl)amino)methyl)piperidin-1-yl)propyl)benzoicAcid

The compound was synthesized using I-67 following the procedure for thesynthesis of I-120. LC-MS m/z calcd for C₃₀H₄₄N₄O₄, 524.3; found 525.4[M+H]⁺.

I-129JBI-XXX-4-(3-(4-(((tert-butoxycarbonyl)(2-(1-phenyl-1H-pyrazol-4-yl)cyclopropyl)amino)methyl)piperidin-1-yl)propyl)benzoicAcid

The compound was synthesized using I-68 following the procedure for thesynthesis of I-120. LC-MS m/z calcd for C₃₃H₄₂N₄O₄, 558.3; found 559.3[M+H]⁺.

I-1304-(3-(4-(((tert-butoxycarbonyl)(2-(2-methylthiazol-5-yl)cyclopropyl)amino)methyl)piperidin-1-yl)propyl)benzoicAcid

The compound was synthesized using I-69 following the procedure for thesynthesis of I-120. LC-MS m/z calcd for C₂₈H₃₉N₃O₄S, 513.3; found 514.3[M+H]⁺.

I-1314-(3-(4-(((tert-butoxycarbonyl)(2-(pyridin-3-yl)cyclopropyl)amino)methyl)piperidin-1-yl)propyl)benzoicAcid

The compound was synthesized using I-70 following the procedure for thesynthesis of I-120. LC-MS m/z calcd for C₂₉H₃₉N₃O₄, 493.3; found 494.3[M+H]⁺.

I-1334-(3-(4-((tert-butoxycarbonyl)(2-phenylcyclopropyl)amino)piperidin-1-yl)-3-oxopropyl)benzoicAcid

The compound was synthesized using I-83 following the procedure for thesynthesis of I-120. LC-MS m/z calcd for C₂₉H₃₆N₂O₅, 492.2; found 491.2[M−H]⁺.

I-1344-(3-(4-(((tert-butoxycarbonyl)(2-phenylcyclopropyl)amino)methyl)piperidin-1-yl)-3-oxopropyl)benzoicAcid

The compound was synthesized using I-82 following the procedure for thesynthesis of I-120. LC-MS m/z calcd for C₃₀H₃₈N₂O₅, 506.2; found 506.3[M]⁺.

I-1354-(3-(4-(((tert-butoxycarbonyl)(2-(3,4-difluorophenyl)cyclopropyl)amino)methyl)-1H-imidazol-1-yl)propyl)benzoicAcid

The compound was synthesized using I-73 following the procedure for thesynthesis of I-120. LC-MS m/z calcd for C₂₈H₃₁F₂N₃O₄, 511.2; found 512.2[M+H]⁺.

I-1364-(3-(4-(((tert-butoxycarbonyl)(2-phenylcyclopropyl)amino)methyl)-1H-imidazol-1-yl)propyl)benzoicAcid

The compound was synthesized using I-75 following the procedure for thesynthesis of I-120. LC-MS m/z calcd for C₂₈H₃₃N₃O₄, 475.2; found 476.2[M+H]⁺.

I-1374-(3-(4-(((tert-butoxycarbonyl)(2-phenylcyclopropyl)amino)methyl)-1H-1,2,3-triazol-1-yl)propyl)benzoicAcid

The compound was synthesized using I-77 following the procedure for thesynthesis of I-120. LC-MS m/z calcd for C₂₇H₃₂N₄O₄, 476.2; found 477.2[M+H]⁺.

I-1384-(3-(4-(((tert-butoxycarbonyl)(2-phenylcyclopropyl)amino)methyl)-1H-pyrazol-1-yl)propyl)benzoicAcid

The compound was synthesized using I-76 following the procedure for thesynthesis of I-120. LC-MS m/z calcd for C₂₈H₃₃N₃O₄, 475.2; found 476.3[M+H]⁺.

I-1394-(2-(4-(((tert-butoxycarbonyl)(2-phenylcyclopropyl)amino)methyl)piperidin-1-yl)ethyl)benzoicAcid

The compound was synthesized using I-42 following the procedure for thesynthesis of I-120. LC-MS m/z calcd for C₂₉H₃₈N₂O₄, 478.2; found 479.3[M+H]⁺.

I-1404-((4-(((tert-butoxycarbonyl)((1R,2S)-2-phenylcyclopropyl)amino)methyl)piperidin-1-yl)methyl)benzoicAcid

The compound was synthesized using I-36 following the procedure for thesynthesis of I-120. LC-MS m/z calcd for C₂₈H₃₆N₂O₄, 464.3; found 465.3[M+H]⁺.

I-1414-((4-(((tert-butoxycarbonyl)(2-(4-(1-methyl-6-oxo-1,6-dihydropyridin-3-yl)phenyl)cyclopropyl)amino)methyl)piperidin-1-yl)methyl)benzoicAcid

The compound was synthesized using I-35 following the procedure for thesynthesis of I-120. LC-MS m/z calcd for C₃₄H₄₁N₃O₅, 571.3; found 572.3[M+H]⁺.

I-1424-((4-(((tert-butoxycarbonyl)(2-(4-(1-methyl-1H-pyrazol-4-yl)phenyl)cyclopropyl)amino)methyl)piperidin-1-yl)methyl)benzoicAcid

The compound was synthesized following the procedure for the synthesisof intermediate I-120 using the corresponding ester (ester wassynthesized using B-7 and methyl4-((4-formylpiperidin-1-yl)methyl)benzoate using the procedure outlinedfor synthesis of I-2). LC-MS m/z calcd for C₃₂H₄₀N₄O₄, 544.3; found545.3 [M+H]⁺.

I-1434-((4-(((tert-butoxycarbonyl)(2-(4-(3,5-dimethylisoxazol-4-yl)phenyl)cyclopropyl)amino)methyl)piperidin-1-yl)methyl)benzoicAcid

The compound was synthesized using I-37 following the procedure for thesynthesis of I-120. LC-MS m/z calcd for C₃₃H₄₁N₃O₅, 559.3; found 560.3[M+H]⁺.

I-1444-((4-(((tert-butoxycarbonyl)(2-(4-(pyrimidin-5-yl)phenyl)cyclopropyl)amino)methyl)piperidin-1-yl)methyl)benzoicAcid

The compound was synthesized using I-38 following the procedure for thesynthesis of I-120. LC-MS m/z calcd for C₃₂H₃₈N₄O₄, 542.2; found 543.3[M+H]⁺.

I-1454-((4-(((tert-butoxycarbonyl)(2-phenylcyclopropyl)amino)methyl)-1H-pyrazol-1-yl)methyl)benzoicAcid

The compound was synthesized using I-40 following the procedure for thesynthesis of I-120. LC-MS m/z calcd for C₂₆H₂₉N₃O₄, 447.2; found 448.2[M+H]⁺.

I-1464-((4-(((tert-butoxycarbonyl)(2-phenylcyclopropyl)amino)methyl)-1H-1,2,3-triazol-1-yl)methyl)benzoicAcid

The compound was synthesized using I-41 following the procedure for thesynthesis of I-120. LC-MS m/z calcd for C₂₅H₂₈N₄O₄, 448.2; found 449.2[M+H]⁺.

I-1474-(2-(4-(((tert-butoxycarbonyl)(2-(4-fluorophenyl)cyclopropyl)amino)methyl)piperidin-1-yl)-2-oxoethyl)benzoicAcid

The compound was synthesized following the procedure for the synthesisof intermediate I-120 using the corresponding ester (ester wassynthesized using 4-fluorocyclopropylamine and aldehyde A-24 using theprocedure outlined for synthesis of I-2). LC-MS m/z calcd forC₂₉H₃₅FN₂O₅, 510.2; found 455.2 [M-55]⁺.

I-1484-(2-((tert-butoxycarbonyl)(2-(4-fluorophenyl)cyclopropyl)amino)ethoxy)benzoicAcid

The compound was synthesized following the procedure for the synthesisof intermediate I-120 using the corresponding ester (ester wassynthesized using 4-fluorocyclopropylamine and LXXVI, using theprocedure outlined for synthesis of I-95). LC-MS m/z calcd forC₂₃H₂₆FNO₅, 415.2; found 416.2 [M+H]⁺.

I-1496-(2-(4-(((tert-butoxycarbonyl)(2-(4-fluorophenyl)cyclopropyl)amino)methyl)piperidin-1-yl)ethoxy)nicotinicacid

The compound was synthesized using I-95 following the procedure for thesynthesis of I-120. LC-MS m/z calcd for C₂₈H₃₆FN₃O₅, 513.2; found514.3[M+H]⁺.

I-1502-((2-(4-(((tert-butoxycarbonyl)(2-(4-fluorophenyl)cyclopropyl)amino)methyl)piperidin-1-yl)ethyl)amino)pyrimidine-5-carboxylicacid

The compound was synthesized using I-101 following the procedure for thesynthesize of I-120. LC-MS m/z calcd for C₂₇H₃₆FN₅O₄, 513.3; found 512.3[M−H]⁺.

I-1515-(N-(tert-butoxycarbonyl)-N-(2-(4-fluorophenyl)cyclopropyl)glycyl)-4,5,6,7-tetrahydrothieno[3,2-c]pyridine-2-carboxylicAcid

The compound was synthesized using I-102 following the procedure for thesynthesis of I-120. LC-MS m/z calcd for C₂₄H₂₇FN₂O₅S, 474.2; found 475.2[M+H]⁺.

I-1522-(N-(tert-butoxycarbonyl)-N-(2-(4-fluorophenyl)cyclopropyl)glycyl)-1,2,3,4-tetrahydroisoquinoline-7-carboxylicAcid

The compound was synthesized using I-103 following the procedure for thesynthesis of I-120. LC-MS m/z calcd for C₂₆H₂₉FN₂O₅, 468.2; found 469.2[M+H]⁺.

I-1532-(3-(4-(((tert-butoxycarbonyl)(2-phenylcyclopropyl)amino)methyl)piperidin-1-yl)propyl)oxazole-4-carboxylicacid

The compound was synthesized using I-112 following the procedure for thesynthesis of I-120. LC-MS m/z calcd for C₂₇H₃₇N₃O₅, 483.2; found 484.2[M+H]⁺.

I-1542-(3-(4-(((tert-butoxycarbonyl)(2-phenylcyclopropyl)amino)methyl)piperidin-1-yl)propyl)thiazole-5-carboxylic

The compound was synthesized using I-111 following the procedure for thesynthesis of I-120. LC-MS m/z calcd for C₂₇H₃₇N₃O₄S, 499.2; found 500.3[M+H]⁺.

I-1554-((2-((tert-butoxycarbonyl)(2-(4-fluorophenyl)cyclopropyl)amino)acetamido)methyl)benzoicAcid

This compound I-155 was synthesized following the procedure for thesynthesis of I-120 using the corresponding ester (ester was synthesizedusing2-((tert-butoxycarbonyl)(2-(4-fluorophenyl)cyclopropyl)amino)acetic acidand methyl 4-(aminomethyl)benzoate using the procedure outlined forsynthesis of I-103). LC-MS m/z calcd for C₂₄H₂₇FN₂O₅, 442.2; found 443.2[M+H]⁺.

I-156(E)-4-(3-(4-(((tert-butoxycarbonyl)(2-(4-fluorophenyl)cyclopropyl)amino)methyl)piperidin-1-yl)-3-oxoprop-1-en-1-yl)benzoicacid

The compound was synthesized using I-114 following the procedure for thesynthesis of I-120. LC-MS m/z calcd for C₃₀H₃₅FN₂O₅, 522.2; found 523.4[M+H]⁺.

I-157(E)-4-(3-(3-(((2-(4-fluorophenyl)cyclopropyl)amino)methyl)azetidin-1-yl)-3-oxoprop-1-en-1-yl)benzoicacid

The compound was synthesized using I-117 following the procedure for thesynthesis of I-120. LC-MS m/z calcd for C₂₃H₂₃FN₂O₃, 394.1; found 395.2[M+H]⁺.

I-1584-((4-(((tert-butoxycarbonyl)(2-(4-fluorophenyl)cyclopropyl)amino)methyl)piperidine-1-carboxamido)methyl)benzoicAcid

Step 1: methyl4-((4-(hydroxymethyl)piperidine-1-carboxamido)methyl)benzoate-LXXXIII

To a stirred solution of methyl 4-(aminomethyl)benzoate (1.0 g, 6.06mmol) in water was added carbonyldiimidazole (1.18 g, 7.26 mmol) 0° C.and stirred for 1 h and then warmed to room temperature. Thenpiperidine-4-ylmethanol (0.84 g, 7.26 mmol) was added and stirringcontinued for 12 h. The resultant white precipitate was filtratedthrough sintered funnel. The filtrate was extracted with dichloromethane(2×100 mL) and the combined organic portion was washed with water,brine, dried over sodium sulphate and concentrated under reducedpressure to get the product as off-white solid (LXXXIII, 0.26 g, 49%).LC-MS m/z calcd for C₁₆H₂₂N₂O₄, 306.1; found 307.2 [M+H]⁺.

Step 2: methyl4-((4-formylpiperidine-1-carboxamido)methyl)benzoate-LXXXIV

To a stirred solution of dimethyl sulphoxide (0.55 ml, 7.84 mmol) indichloromethane oxalyl chloride (0.45 mL, 5.22 mmol) was slowly added at−78° C. After 30 min stirring, a solution of methyl4-((4-(hydroxymethyl)piperidine-1-carboxamido)methyl)benzoate (LXXXIII,0.4 g, 1.30 mmol) was added dropwise. Then the reaction mixture wasstirred for 3 h at −78° C. Triethylamine (2.1 mL, 15.68 mmol) was addedand stirred for 0.5 h. The reaction mixture was allowed to warm to roomtemperature. The reaction mixture was diluted with dichloromethane,washed with water, brine, dried over sodium sulphate and concentratedunder reduced pressure to get the product as yellow brown oil (LXXXIV,0.35 g, 89%). LC-MS m/z calcd for C₁₆H₂₀N₂O₄, 304.1; found 305.1 [M+H]⁺.

Step 3: methyl4-((4-(((tert-butoxycarbonyl)(2-(4-fluorophenyl)cyclopropyl)amino)methyl)piperidine-1-carboxamido)methyl)benzoate-LXXXV

To a stirred solution of 2-(4-flurophenyl)cyclopropylamine hydrochloride(0.2 g, 1.06 mmol) in methanol (15 mL) was added methyl4-((4-formylpiperidine-1-carboxamido)methyl)benzoate (LXXXIV, 0.39 g,1.28 mmol), sodium bicarbonate (0.08 g, 0.95 mmol), and molecular sieves(approx 1 g) at room temperature and the resulting mixture was heated toreflux for 2 h. The reaction mixture was cooled to 0° C. and sodiumborohydride (0.35 g, 0.95 mmol) was added. Stirring was continued atroom temperature for 1 h. Ice-water was added and the reaction mixturewas filtered. The solvent was evaporated to get the residue. Water wasadded to the residue and extracted with dichloromethane (2×50 mL). Thecombined organic portion were washed with water, brine, dried oversodium sulphate and concentrated under reduced pressure to afford thecrude product as brown oil (0.44 g). The crude product was dissolvedintetrahydrofuran-water mixture (20 mL, 1:1). Sodium bicarbonate (0.26g, 3.07 mmol) and Boc anhydride (0.26 mL, 1.25 mmol) were added at roomtemperature. The resulting mixture was stirred at that temperature for 1h. The reaction mixture was diluted with ethylacetate and was washedwith water, brine solution, dried over sodium sulphate and concentratedunder reduced pressure to get the crude product which was purified bycolumn chromatography using methanol-dichloromethane gradient to affordthe titled product as brown thick oil (LXXXV, 0.22 g, 40%). LC-MS m/zcalcd for C₃₀H₃₈FN₃O₅, 539.3; found 540.3 [M+H]⁺.

Step 4:4-((4-(((tert-butoxycarbonyl)(2-(4-fluorophenyl)cyclopropyl)amino)methyl)piperidine-1-carboxamido)methyl)benzoic Acid (Intermediate I-158)

To a stirred solution of methyl4-((4-(((tert-butoxycarbonyl)(2-(4-fluorophenyl)cyclopropyl)amino)methyl)piperidine-1-carboxamido)methyl)benzoate(LXXXV, 0.22 g, 0.40 mmol), in mixture of tetrahydrofuran-water (6 mL,1:1), and lithium hydroxide (0.029 g, 1.22 mmol) was added and stirredfor 1 h at room temperature. After completion of the reaction, themixture was evaporated, the residue was diluted with ice-water, andacidified to pH 5 with 2N HCl. The aqueous layer was extracted withdichloromethane (50 mL×2). The combined organic layer was washed withwater, brine, dried over sodium sulphate and concentrated under reducedpressure to get the product as off-white solid (I-158, 0.22 g,quantitative yield). LC-MS m/z calcd for C₂₉H₃₆FN₃O₅, 525.2; found 526.2[M+H]⁺.

I-1594-(3-(4-(((tert-butoxycarbonyl)(2-phenylcyclopropyl)amino)methyl)-2-oxopiperidin-1-yl)propyl)benzoicAcid

The compound was synthesized using I-93 following the procedure for thesynthesis of I-120. LC-MS m/z calcd for C₃₀H₃₈N₂O₅, 506.2; found 507.2[M+H]⁺.

I-1604-((4-(((tert-butoxycarbonyl)(2-phenylcyclopropyl)amino)methyl)piperidin-1-yl)sulfonyl)benzoicacid

I-1604-((4-((2,2,2-trifluoro-N-(2-phenylcyclopropyl)acetamido)methyl)piperidin-1-yl)sulfonyl)benzoic Acid

To a stirred solution of2,2,2-trifluoro-N-(2-phenylcyclopropyl)-N-(piperidin-4-ylmethyl)acetamide(1 g, 2.7 mmol) in dichloromethane (20 mL) was added triethylamine (1.1mL, 8.10 mmol) and 4-(chlorosulfonyl)benzoic acid (0.66 g, 2.7 mmol) at0° C. and stirred at room temperature for 2 h. The reaction mixture wasconcentrated under vacuum. Then the resultant residue was mixed withtetrahydrofuran-water (20 mL, 1:1) and lithium hydroxide (0.28 g, 6.7mmol) was added at room temperature. After stirring for 3 h, Bocanhydride (0.88 mL, 4 mmol) was added and stirring continued for 2 h atroom temperature. The solvent was evaporated and the residue wasacidified with 2N HCl and extracted with dichloromethane. The combinedorganic portion was washed with water, brine, dried over sodium sulphateand concentrated under reduced pressure to afford the titled product asoff-white solid (I-160, 1.2 g, 84%). LC-MS m/z calcd for C₂₇H₃₄N₂O₆S,514.2; found 415.1 [M-Boc+H]⁺.

I-1614-(((4-(((tert-butoxycarbonyl)(2-phenylcyclopropyl)amino)methyl)piperidin-1-yl)sulfonyl)methyl)benzoicacid-ester Procedure

Step-1

The compound was synthesized using amine B-3 and methyl4-((chlorosulfonyl)methyl)benzoate following the procedure for thesynthesis of I-85.

Step-2

Hydrolysis of ester LXXXVI, followed by protection with (Boc)₂O resultedin I-161 as white solid. LC-MS m/z calcd for C₂₈H₃₆N₂O₆S, 528.2; found529.2 [M+H]⁺.

I-1624-(2-((4-(((tert-butoxycarbonyl)(2-phenylcyclopropyl)amino)methyl)piperidin-1-yl)sulfonyl)ethyl)benzoicacid

The compound was synthesized using I-88 following the procedure for thesynthesis of I-120. LC-MS m/z calcd for C₂₉H₃₈N₂O₆S, 542.2; found 543.2[M+H]⁺.

Example 1 Synthesis of(E)-3(4(((2(4cyclopropylphenyl)cyclopropl)amino)methyl)phenyl)-N-hydroxyacrylamide(XLIV)

Step-1:(E)-3-(4-{[2-(4-Cyclopropyl-phenyl)-cyclopropylamino]-methyl}-phenyl)-acrylicAcid Methyl Ester (LXXXVIII)

2-(4-Cyclopropyl-phenyl)-cyclopropylamine.HCl (LXXXVII, 0.3 g, 1.43mmol); which was prepared through cycloproponation of alkene (asdescribed in Bioorg. Med. Chem. Lett., 2008, 18, 3047-3051) wasdissolved in dichloroethane and triethylamine (approx 1 mL) was addedand stirred for 5 min. The solvent was concentrated under reducedpressure to get the free amine. To a stirred solution of(E)-3-(4-formyl-phenyl)-acrylic acid methyl ester (0.22 g, 1.19 mmol)which was synthesized using reported procedure (J. Org. Chem., 2011,76(19), 8036-8041) in 1,2-dichloroethane (20 mL) was added to the freecyclopropylamine and the resulting mixture was stirred at 60° C. for 1h. Cooled to 0° C., sodium triacetoxyborohydride (0.5 g, 2.39 mmol) wasadded and the resulting mixture was stirred at room temperature for 12h. The reaction mixture was filtered and the filtrate was diluted withdichloromethane (50 mL). The organic portion was washed with water andbrine dried over sodium sulphate and concentrated under reduced pressureto afford the crude. The crude product was purified by columnchromatography using ethylacetate-hexane gradient to obtain titledcompound as gummy oil (LXXXVIII, 0.22 g, 55%), LC-MS m/z calcd forC₂₃H₂₅NO₂, 347.1; found 348.2 [M+H]⁺.

Step-2:(E)-3-(4-{[2-(4-Cyclopropyl-phenyl)-cyclopropylamino]-methyl}-phenyl)-N-hydroxy-acrylamide—Example1

Example 1

To a solution of hydroxylamine hydrochloride (0.79 g, 11.41 mmol) inmethanol (5 mL) was added a solution of potassium hydroxide (0.64 g,11.41 mmol) in methanol (5 mL) at 5-10° C. and stirred at thattemperature for 15 min. The formed precipitate was filtered throughcotton plug and the filtrate was added to a solution of(E)-3-(4-{[2-(4-cyclopropyl-phenyl)-cyclopropylamino]-methyl}-phenyl)-acrylicacid methyl ester (LXXXVIII, 0.22 g, 0.63 mmol) in methanol at roomtemperature. The resulting mixture was stirred at room temperature for 3h. The reaction mixture was diluted with water and extracted withethylacetate (3×50 mL). The combined organic extract was dried oversodium sulphate and concentrated under reduced pressure to afford thecrude product. The crude product was purified through trituration withacetonitrile solvent to afford the titled compound as an off-white solid(Example 1, 0.28 g, 13%). ¹HNMR (400 MHz, DMSO-d₆): δ 10.7 (bs, 1H),8.98 (bs, 1H), 7.46-7.36 (m, 3H), 7.32 (d, 2H, J=8 Hz), 6.88 (d, 2H,J=7.6 Hz), 6.83 (d, 2H, J=8 Hz), 6.41 (d, 1H, J=16 Hz), 3.75 (s, 2H),2.91-2.75 (m, 1H), 2.17-2.10 (m, 1H), 1.85-1.72 (m, 2H), 0.96-0.91 (m,1H), 0.88-0.82 (m, 3H), 0.58-0.53 (m, 2H). LC-MS m/z calcd forC₂₂H₂₄N₂O₂, 348.1; found 349.2 [M+H]⁺. HPLC purity 98.6%.

Example 2(E)-3-(4-{[2-(4-Fluoro-phenyl)-cyclopropylamino]-methyl}-phenyl)-N-hydroxy-acrylamideTFA Salt

Step 1:[2-(4-Fluoro-phenyl)-cyclopropyl]-[4-((E)-2-hydroxycarbamoyl-vinyl)-benzyl]-carbamicAcid Tert-Butyl Ester (LXXXIX)

To a solution of hydroxylamine hydrochloride (0.147 g, 2.11 mmol) inmethanol was added a solution of potassium hydroxide (0.12 g, 2.11 mmol)in methanol at 5-10° C. and stirred at that temperature for 15 min. Theformed precipitate was filtered through cotton plug and the filtrate wasadded to a solution of(E)-3-[4-({tert-butoxycarbonyl-[2-(4-fluoro-phenyl)-cyclopropyl]-amino}-methyl)-phenyl]-acrylicacid methyl ester (I-2, 0.05 g, 0.12 mmol) in methanol (4 mL) at roomtemperature. Potassium hydroxide (0.12 g, 2.11 mmol) was added and theresulting mixture was stirred at room temperature for 1 h. The solventwas removed and water was added to the resulting residue. The pH of theaqueous portion was adjusted to 7.0 with 10% acetic acid solution andthen extracted with ethylacetate (3×30 mL). The combined organic extractwas washed with brine, dried over sodium sulphate and concentrated underreduced pressure to afford the crude product which was triturated withwater and dried to afford the title compound as a white solid (LXXXIX,0.035 g, 73%). LC-MS m/z calcd for C₂₄H₂₇FN₂O₄, 426.2; found 427.2[M+H]⁺.

Step 2:(E)-3-(4-{[2-(4-Fluoro-phenyl)-cyclopropylamino]-methyl}-phenyl)-N-hydroxy-acrylamide.TFA Salt—Example 2

To a stirred solution of[2-(4-fluoro-phenyl)-cyclopropyl]-[4-((E)-2-hydroxycarbamoyl-vinyl)-benzyl]-carbamicacid tert-butyl ester (LXXXIX, 0.15 g, 0.36 mmol) in dry dichloromethane(2 mL) was added trifluoroacetic acid (2 mL) at 0° C. and the resultingmixture was stirred at that temperature for 1 h. The progress of thereaction was monitored by TLC. The solvent was concentrated underreduced pressure to get the crude product which was purified byreverse-phase HPLC using Chemsil C₁₈ (250 mm×4.6 mm×5mic) column with0.1% TFA in water:ACN to afford the pure product as off-white solid(Example 2, 0.04 g, 26%).

¹HNMR (400 MHz, DMSO-d₆): δ 10.76 (bs, 1H), 9.18 (bs, 1H), 9.04 (bs,1H), 7.59 (d, 2H, J=7.6 Hz), 7.52-7.42 (m, 3H), 7.18-7.07 (m, 4H), 6.48(d, 1H, J=16 Hz), 4.30 (s, 2H), 2.89 (bs, 1H), 2.41-2.32 (m, 1H),1.45-1.37 (m, 1H), 1.32-1.25 (m, 1H). LC-MS m/z calcd for C₁₉H₁₉FN₂O₂,326.1; found 327.3 [M+H]⁺. HPLC purity 97.1%.

The following compounds were synthesized using the procedure exemplifiedin Example 2

Example 3(E)-3-(4-(((2-(4-((4-fluorobenzyl)oxy)phenyl)cyclopropyl)amino)methyl)phenyl)-N-hydroxyacrylamideTFA Salt

The compound was synthesized using the I-3 following the procedure forExample 2. ¹HNMR (400 MHz, DMSO-d₆): δ 10.75 (bs, 1H), 9.02 (bs, 1H),7.57-7.55 (m, 2H), 7.49-7.41 (m, 5H), 7.20 (t, 2H, J=9 Hz), 7.00 (d, 2H,J=8.4 Hz), 6.89 (d, 2H, J=8.4 Hz), 6.47 (d, 1H, J=15.6 Hz), 5.04 (s,2H), 4.19-4.14 (m, 2H), 2.76-2.45 (m, 1H), 2.24-2.15 (m, 1H), 1.31-1.22(m, 1H), 1.14-1.10 (m, 1H). LC-MS m/z calcd for C₂₆H₂₅FN₂O₃, 432.1.found 433.2 [M+H]⁺. HPLC purity 96.3%.

Example 4(E)-N-hydroxy-3-(4-(4-(((2-phenylcyclopropyl)amino)methyl)piperidin-1-yl)phenyl)acrylamideTFA Salt

The compound was synthesized using the I-4 following the procedure forExample 2. ¹HNMR (400 MHz, DMSO-d₆): δ 10.53 (bs, 1H), 8.78 (bs, 1H),7.42-7.26 (m, 5H), 7.24-7.15 (m, 3H), 6.94 (d, 2H, J=8.8 Hz), 6.22 (d,1H, J=15.6 Hz), 5.32 (bs, 1H), 3.86-3.80 (m, 2H), 3.65-3.59 (m, 1H),3.15-3.11 (m, 1H), 3.08-2.96 (m, 3H), 2.79-2.70 (m, 2H), 2.02-1.96 (m,1H), 1.90-1.76 (m, 3H), 1.49-1.41 (m, 1H), 0.86-0.80 (m, 1H). LC-MS m/zcalcd for C₂₄H₂₉N₃O₂, 391.2; found 392.3 [M+H]⁺. HPLC purity 99.4%.

Example 5(E)-3-(4-(((2-(4′-chloro-[1,1′-biphenyl]-4-yl)cyclopropyl)amino)methyl)phenyl)-N-hydroxyacrylamideTFA Salt

The compound was synthesized using the I-5 following the procedure forExample 2. ¹HNMR (400 MHz, DMSO-d₆): δ 10.75 (s, 1H), 9.20 (bs, 1H),9.03 (s, 1H), 7.66 (d, 2H, J=8.4 Hz), 7.61-7.56 (m, 4H), 7.50-7.42 (m,5H), 7.21-7.19 (m, 2H), 6.48 (d, 1H, J=16 Hz), 4.32-4.25 (m, 2H),1.48-1.32 (m, 2H), 1.25-1.15 (m, 2H). LC-MS m/z calcd for C₂₅H₂₃ClN₂O₂,418.1; found 419.2 [M+H]⁺. HPLC purity 92.8%.

Example 6(E)-3-(4-(((2-(4-(3,5-dimethylisoxazol-4-yl)phenyl)cyclopropyl)amino)methyl)phenyl)-N-hydroxyacrylamideTFA Salt

The compound was synthesized using the I-6 following the procedure forExample 2. ¹HNMR (400 MHz, DMSO-d₆): δ 10.74 (s, 1H), 9.25 (bs, 2H),9.02 (bs, 1H), 7.61 (d, J=7.6 Hz, 2H), 7.50 (d, J=8 Hz, 2H), 7.44 (d,J=15.6 Hz, 1H), 7.28 (d, J=8 Hz, 2H), 7.21 (d, J=8 Hz, 2H), 6.47 (d,J=16 Hz, 1H), 4.32 (s, 2H), 2.96 (m, 1H), 2.55 (m, 1H), 2.36 (s, 3H),2.18 (s, 3H), 1.50-1.40 (m, 1H), 1.40-1.30 (m, 1H). LC-MS m/z calcd forC₂₄H₂₅N₃O₃, 403.2; found 404.2 [M+H]⁺. HPLC purity 98.8%.

Example 7(E)-N-hydroxy-3-(4-(((2-(4-(pyrimidin-5-yl)phenyl)cyclopropyl)amino)methyl)phenyl)acrylamideTFA Salt

The compound was synthesized using the I-7 following the procedure forExample 2. ¹HNMR (400 MHz, DMSO-d₆): δ 10.76 (s, 1H), 9.36 (bs, 2H),9.25 (bs, 1H), 9.16 (s, 1H), 9.12 (s, 2H), 7.74 (d, J=8.4 Hz, 2H), 7.60(d, J=8.0 Hz, 2H), 7.50 (d, J=8.0 Hz, 2H), 7.45 (d, J=15.6 Hz, 1H), 7.29(d, J=8.0 Hz, 2H), 6.48 (d, J=15.6 Hz, 1H), 4.34 (s, 2H), 3.02 (m, 1H),2.55 (m, 1H), 1.52-1.42 (m, 1H), 1.42-1.34 (m, 1H). LC-MS m/z calcd forC₂₃H₂₂N₄O₂, 386.2; found 387.2 [M+H]⁺. HPLC purity 98.3%.

Example 82-(4-(((2-(4-fluorophenyl)cyclopropyl)amino)methyl)piperidin-1-yl)-N-hydroxypyrimidine-5-carboxamideTFA Salt

The compound was synthesized using the I-8 following the procedure forExample 2. ¹HNMR (400 MHz, DMSO-d₆): δ 11.02 (s, 1H), 8.75 (bs, 2H),8.64 (s, 2H), 7.23-7.20 (dd, J=5.6, 5.6 Hz, 2H), 7.14-7.10 (dd, J=9.2,8.8 Hz, 2H), 4.70-4.67 (d, J=13.6 Hz, 2H), 3.01-2.92 (m, 5H), 2.44-2.41(m, 1H), 2.05-1.95 (m, 1H), 1.82-1.79 (m, 2H), 1.47-1.42 (m, 1H),1.30-1.25 (q, 1H), 1.20-1.12 (m, 2H). LC-MS m/z calcd [M+H]⁺ 385.2.found 386.2. HPLC purity 99.8%.

Example 92-[4-(2-Phenyl-cyclopropylamino)-piperidin-1-yl]-pyrimidine-5-carboxylicAcid Hydroxyamide TFA Salt

The compound was synthesized using the I-9 following the procedure forExample 2. ¹HNMR (400 MHz, DMSO-d₆): δ 10.96 (bs, 1H), 8.94 (bs, 1H),7.24-7.18 (m, 2H), 7.12-7.08 (m, 1H), 7.04-7.00 (m, 2H), 4.50-4.4 (m,2H), 3.20-3.10 (m, 2H), 2.90-2.80 (m, 1H), 2.28-2.20 (m, 2H), 1.88-1.75(m, 3H), 1.28-1.16 (m, 2H), 0.98-0.92 (m, 2H), 0.86-0.81 (m, 1H). LC-MSm/z calcd for C₁₉H₂₃N₅O₂, 353.2; found 354.2 [M+H]⁺. HPLC purity 99.8%.

Example 102-{4-[2-(4-Fluoro-phenyl)-cyclopropylamino]-piperidin-1-yl}-pyrimidine-5-carboxylicacid hydroxyamide TFA salt

The compound was synthesized using the I-10 following the procedure forExample 2. ¹HNMR (400 MHz, DMSO-d₆): δ 10.95 (bs, 1H), 8.93 (bs, 1H),8.63 (s, 2H), 7.09-7.01 (m, 4H), 4.50-4.41 (m, 2H), 3.18-3.08 (m, 2H),2.88-2.80 (m, 1H), 2.25-2.18 (m, 1H), 1.86-1.75 (m, 3H), 1.28-1.15 (m,3H), 0.99-0.89 (m, 2H). LC-MS m/z calcd for C₁₉H₂₂FN₅O₂, 371.1; found372.1 [M+H]⁺. HPLC purity 97.7%.

Example 112-(4-(((2-(4-((4-fluorobenzyl)oxy)phenyl)cyclopropyl)amino)methyl)piperidin-1-yl)-N-hydroxypyrimidine-5-carboxamideTFA Salt

The compound was synthesized using the I-11 following the procedure forExample 2. ¹HNMR (400 MHz, DMSO-d₆): δ 11.03 (bs, 1H), 8.97 (bs, 1H),8.72 (bs, 2H), 8.66 (s, 2H), 7.48-7.45 (m, 2H), 7.23-7.18 (m, 2H), 7.11(d, 2H, J=8.4 Hz), 6.94 (d, 2H, J=8 Hz), 5.06 (s, 2H), 4.71 (d, 2H,J=12.4 Hz), 3.08-2.85 (m, 6H), 2.40-2.34 (m, 2H), 2.05-1.94 (m, 1H),1.84-1.77 (m, 2H), 1.42-1.36 (m, 1H), 1.24-1.11 (m, 1H). LC-MS m/z calcdfor C₂₇H₃₀FN₅O₃, 491.2; found 492.4 [M+H]⁺. HPLC purity 96.7%.

Example 122-(4-((2-(4-((4-fluorobenzyl)oxy)phenyl)cyclopropyl)amino)piperidin-1-yl)-N-hydroxypyrimidine-5-carboxamideTFA Salt

The compound was synthesized using the I-12 following the procedure forExample 2. ¹HNMR (400 MHz, DMSO-d₆): δ 11.07 (bs, 1H), 9.0 (bs, 1H),8.88 (bs, 1H), 8.84 (bs, 1H), 8.69 (s, 2H), 7.49-7.35 (m, 2H), 7.20 (t,2H, J=8.8 Hz), 7.11 (d, 2H, J=8.4 Hz), 6.94 (d, 2H, J=8.4 Hz), 5.06 (s,2H), 4.77 (d, 2H, J=12.8 Hz), 3.63-3.54 (m, 1H), 3.05-2.90 (m, 4H),2.14-2.08 (m, 2H), 1.52-1.44 (m, 2H), 1.39-1.32 (m, 1H), 1.30-1.23 (m,1H). LC-MS m/z calcd for C₂₆H₂₈FN₅O₃, 477.2; found 476.2 [M−H]⁺. HPLCpurity 99.7%.

Example 132-(4-((2-(4′-chloro-[1,1′-biphenyl]-4-yl)cyclopropyl)amino)piperidin-1-yl)-N-hydroxypyrimidine-5-carboxamideTFA Salt

The compound was synthesized using the I-13 following the procedure forExample 2. ¹HNMR (400 MHz, DMSO-d₆): δ 11.07 (s, 1H), 9.01-8.96 (m, 3H),8.68 (s, 2H), 7.67 (d, 2H, J=8.4 Hz), 7.61 (d, 2H, J=8.0 Hz), 7.50 (d,2H, J=8.4 Hz), 7.29 (d, 2H, J=7.6 Hz), 4.78 (d, 2H, J=12.8 Hz), 3.60(bs, 1H), 3.02 (t, 4H, J=12.4 Hz), 2.13 (d, 2H, J=10.8 Hz), 1.50-1.47(m, 3H), 1.40-1.38 (m, 1H). LC-MS m/z calcd for C₂₅H₂₆ClN₅O₂, 464.1;found 464.2 [M+H]⁺. HPLC purity 98.8%.

Example 142-(4-(((2-(4′-chloro-[1,1′-biphenyl]-4-yl)cyclopropyl)amino)methyl)piperidin-1-yl)-N-hydroxypyrimidine-5-carboxamideTFA Salt

The compound was synthesized using the I-14 following the procedure forExample 2. ¹HNMR (400 MHz, DMSO-d₆): δ 11.03 (bs, 1H), 8.97 (bs, 1H),8.89 (bs, 2H), 8.66 (s, 2H), 7.67 (d, 2H, J=11.2 Hz), 7.61 (d, 2H, J=8Hz), 7.49 (d, 2H, J=8 Hz), 7.28 (d, 2H, J=7.6 Hz), 4.71 (d, 2H, J=13.2Hz), 3.09-2.91 (m, 5H), 2.09-1.96 (m, 1H), 1.86-1.78 (m, 2H), 1.52-1.48(m, 1H), 1.41-1.31 (m, 1H), 1.27-1.12 (m, 3H). LC-MS m/z calcd forC₂₆H₂₈ClN₅O₂, 477.1; found 476.4 [M−H]⁺. HPLC purity 98.8%.

Example 152-(4-(((2-(4′-fluoro-[1,1′-biphenyl]-4-yl)cyclopropyl)amino)methyl)piperidin-1-yl)-N-hydroxypyrimidine-5-carboxamideTFA Salt

The compound was synthesized using the I-15 following the procedure forExample 2. ¹HNMR (400 MHz, DMSO-d₆): δ 11.02 (bs, 1H), 8.96 (bs, 1H),8.80 (bs, 1H), 8.73 (bs, 1H), 8.65 (s, 2H), 7.69-7.64 (m, 2H), 7.59-7.55(m, 2H), 7.28-7.23 (m, 4H), 4.74-4.55 (m, 2H), 3.08-2.93 (m, 6H),2.05-1.96 (m, 1H), 1.84-1.80 (m, 2H), 1.51-1.44 (m, 1H), 1.36-1.32 (m,1H), 1.24-1.15 (m, 2H). LC-MS m/z calcd for C₂₆H₃₈FN₅O₂, 461.2; found462.2 [M+H]⁺. HPLC purity 99.5%.

Example 162-(4-(((2-(4-(3,5-dimethylisoxazol-4-yl)phenyl)cyclopropyl)amino)methyl)piperidin-1-yl)-N-hydroxypyrimidine-5-carboxamideTFA Salt

The compound was synthesized using the I-16 following the procedure forExample 2. ¹HNMR (400 MHz, DMSO-d₆): δ 11.02 (bs, 1H), 8.95 (bs, 1H),8.85 (bs, 1H), 8.73 (bs, 1H), 8.65 (s, 2H), 7.31-7.26 (m, 4H), 4.69 (d,J=12.8 Hz, 2H), 3.08-2.92 (m, 5H), 2.55 (m, 1H), 2.35 (s, 3H), 2.18 (s,3H), 2.06-1.95 (m, 1H), 1.85-1.78 (m, 2H), 1.53-1.45 (m, 1H), 1.40-1.32(m, 1H), 1.25-1.10 (m, 2H). LC-MS m/z calcd for C₂₅H₃₀N₆O₃, 462.2; found463.2 [M+H]⁺. HPLC purity 99.1%.

Example 17N-hydroxy-2-(4-(((2-(4-(pyrimidin-5-yl)phenyl)cyclopropyl)amino)methyl)piperidin-1-yl)pyrimidine-5-carboxamideTFA Salt

The compound was synthesized using the I-17 following the procedure forExample 2. ¹HNMR (400 MHz, DMSO-d₆): δ 11.02 (bs, 1H), 9.16 (s, 1H),9.12 (s, 2H), 8.90 (bs, 2H), 8.83 (bs, 1H), 8.65 (s, 2H), 7.76 (d, J=8.4Hz, 2H), 7.35 (d, J=8 Hz, 2H), 4.73-4.67 (m, 2H), 3.08-2.93 (m, 5H),2.08-1.92 (m, 2H), 1.84-1.78 (m, 2H), 1.54-1.50 (m, 1H), 1.42-1.35 (m,1H), 1.25-1.13 (m, 2H). LC-MS m/z calcd for C₂₄H₂₇N₇O₂, 445.2. found446.2 [M+H]⁺. HPLC purity 99.8%.

Example 18N-hydroxy-2-(4-(((2-(4-methoxyphenyl)cyclopropyl)amino)methyl)piperidin-1-yl)pyrimidine-5-carboxamideTFA Salt

The compound was synthesized using the I-18 following the procedure forExample 2. ¹HNMR (400 MHz, DMSO-d₆): δ 11.03 (bs, 1H), 8.96 (bs, 1H),8.79 (bs, 2H), 8.68 (s, 2H), 7.10 (d, 2H, J=8.4 Hz), 6.86 (d, 2H, J=8.8Hz), 4.77 (d, 2H, J=13.2 Hz), 3.71 (s, 3H), 3.05-2.85 (m, 5H), 2.42-2.32(m, 1H), 2.05-1.97 (m, 1H), 1.83-1.80 (m, 2H), 1.42-1.37 (m, 1H),1.24-1.13 (m, 3H). LC-MS m/z calcd for C₂₁H₂₇N₅O₃, 397.2; found 398.2[M+H]⁺. HPLC purity 96.2%.

Example 19N-hydroxy-2-(4-((2-(4-methoxyphenyl)cyclopropyl)amino)piperidin-1-yl)pyrimidine-5-carboxamideTFA Salt

The compound was synthesized using the I-19 following the procedure forExample 2. ¹HNMR (400 MHz, DMSO-d₆): δ 11.06 (bs, 1H), 9.04 (bs, 2H),8.67 (s, 2H), 7.19 (d, 2H, J=8.4 Hz), 6.85 (d, 2H, J=9.2 Hz), 4.78-4.73(m, 2H), 3.70 (s, 3H), 3.61-3.53 (m, 1H), 3.03-2.96 (m, 2H), 2.92-2.84(m, 1H), 2.35-2.30 (m, 1H), 2.11-2.04 (m, 2H), 1.51-1.45 (m, 2H),1.40-1.34 (m, 1H), 1.27-1.21 (m, 1H). LC-MS m/z calcd for C₂₀H₂₅N₅O₃,383.2; found 384.2 [M+H]⁺. HPLC purity 97.1%.

Example 202-(4-((((1R,2S)-2-(4-fluorophenyl)cyclopropyl)amino)methyl)piperidin-1-yl)-N-hydroxypyrimidine-5-carboxamideTFA Salt

The compound was synthesized using the I-20 following the procedure forExample 2. ¹HNMR (400 MHz, DMSO-d₆): δ 11.02 (bs, 1H), 8.95 (bs, 1H),8.64 (s, 2H), 7.22-7.15 (m, 2H), 7.13-7.06 (m, 2H), 4.72-4.62 (m, 2H),3.01-2.92 (m, 4H), 2.89-2.81 (m, 1H), 2.35-2.28 (m, 1H), 2.00-1.91 (m,1H), 1.84-1.76 (m, 2H), 1.40-01.38 (m, 1H), 1.35-1.09 (m, 3H). LC-MS m/zcalcd for C₂₀H₂₄FN₅O₂[M+H]⁺ 385.1. found 386.2. HPLC purity 98.2%.

Example 212-(4-((((1S,2R)-2-(4-fluorophenyl)cyclopropyl)amino)methyl)piperidin-1-yl)-N-hydroxypyrimidine-5-carboxamideTFA Salt

The compound was synthesized using the I-21 following the procedure forExample 2. ¹HNMR (400 MHz, DMSO-d₆): δ 11.02 (bs, 1H), 8.95 (bs, 1H),8.64 (s, 2H), 7.22-7.15 (m, 2H), 7.13-7.06 (m, 2H), 4.72-4.62 (m, 2H),3.01-2.92 (m, 4H), 2.89-2.81 (m, 1H), 2.35-2.28 (m, 1H), 2.00-1.91 (m,1H), 1.84-1.76 (m, 2H), 1.40-01.38 (m, 1H), 1.35-1.09 (m, 3H). LC-MS m/zcalcd for C₂₀H₂₄FN₅O₂[M+H]⁺ 385.1. found 386.1. HPLC purity 98.1%.

Example 224-(4-(((2-(4-fluorophenyl)cyclopropyl)amino)methyl)piperidin-1-yl)-N-hydroxybenzamideTFA Salt

The compound was synthesized using the I-22 following the procedure forExample 2. ¹HNMR (400 MHz, DMSO-d₆): δ 10.98 (bs, 1H), 8.82 (bs, 2H),7.61 (d, 2H, J=8.4 Hz), 7.24-7.20 (m, 2H), 7.16-7.08 (m, 2H), 6.92 (d,2H, J=8.4 Hz), 3.95-3.80 (m, 2H), 3.04-2.90 (m, 3H), 2.79-2.70 (m, 2H),2.42-2.35 (1H, m), 1.87-1.77 (m, 3H), 1.46-1.41 (m, 1H), 1.34-1.20 (m,3H). LC-MS m/z calcd for C₂₂H₂₆FN₃O₂, 383.2; found 384.2 [M+H]⁺. HPLCpurity 98.0%.

Example 23N-hydroxy-2-(2-(((2-phenylcyclopropyl)amino)methyl)-5,6-dihydroimidazo[1,2-a]pyrazin-7(8H)-yl)pyrimidine-5-carboxamideTFA Salt

The compound was synthesized using the I-23 following the procedure forExample 2. ¹HNMR (400 MHz, DMSO-d₆): δ 8.71 (s, 2H), 7.22-7.15 (m, 2H),7.09-7.05 (m, 1H), 7.01-6.94 (m, 2H), 6.86 (s, 1H), 4.86 (s, 2H),4.45-4.38 (m, 2H), 4.02-3.93 (m, 2H), 3.61 (s, 2H), 2.30-2.25 (m, 1H),1.82-1.75 (m, 1H), 1.02-0.88 (m, 2H). LC-MS m/z calcd for C₂₁H₂₃N₇O₂,405.1; found 406.2 [M+H]⁺. HPLC purity 98.2%. (3 exchangeable protonmerged with solvent)

Example 24N-hydroxy-2-(2-(((2-(4-methoxyphenyl)cyclopropyl)amino)methyl)-5,6-dihydroimidazo[1,2-a]pyrazin-7(8H)-yl)pyrimidine-5-carboxamideTFA Salt

The compound was synthesized using the I-24 following the procedure forExample 2. ¹HNMR (400 MHz, DMSO-d₆): δ 11.14 (bs, 1H), 9.22 (bs, 2H),8.76 (s, 2H), 7.23 (s, 1H), 6.96 (d, 2H, J=8.4 Hz), 6.77 (d, 2H, J=8.4Hz), 5.03-4.91 (m, 2H), 4.29-4.13 (m, 4H), 4.09-3.98 (m, 2H), 3.67 (s,3H), 2.83-2.78 (m, 1H), 2.25-2.18 (m, 1H), 1.36-1.29 (m, 1H), 1.23-1.13(m, 1H). LC-MS m/z calcd for C₂₂H₂₅N₇O₃, 435.2. found 436.1[M+H]⁺. HPLCpurity 99.6%.

Example 252-(2-(((2-(4-fluorophenyl)cyclopropyl)amino)methyl)-5,6-dihydroimidazo[1,2-a]pyrazin-7(8H)-yl)-N-hydroxypyrimidine-5-carboxamideTFA Salt

The compound was synthesized using the I-25 following the procedure forExample 2. ¹HNMR (400 MHz, DMSO-d₆): δ 11.18 (bs, 1H), 9.28 (bs, 2H),8.75 (s, 2H), 7.24 (s, 1H), 7.12-7.02 (m, 4H), 4.96 (q, 2H, J=17.2 Hz),4.25-4.22 (m, 2H), 4.18-4.14 (m, 2H), 4.11-4.00 (m, 2H), 2.87 (t, 1H,J=3.2 Hz), 2.29 (s, 1H), 1.40-1.35 (m, 1H), 1.23 (t, 1H, J=6.8 Hz).LC-MS m/z calcd for C₂₁H₂₂FN₇O₂, 423.2; found 424.4 [M+H]⁺. HPLC purity99.5%.

Example 263-(((2-(4-bromophenyl)cyclopropyl)amino)methyl)-N-hydroxybenzamide TFASalt

The compound was synthesized using the I-26 following the procedure forExample 2. ¹HNMR (400 MHz, DMSO-d₆): δ 11.09 (bs, 1H), 8.95 (bs, 1H),7.71 (s, 1H), 7.57 (d, 1H, J=7.6 Hz), 7.41 (d, 1H, J=7.6 Hz), 7.35-7.31(m, 3H), 6.92 (d, 2H, J=8.4 Hz), 3.77 (s, 2H), 2.92 (bs, 1H), 2.21-2.17(m, 1H), 1.82-1.78 (m, 1H), 1.04-0.99 (m, 1H), 0.95-0.90 (m, 1H). LC-MSm/z calcd for C₁₇H₁₇BrN₂O₂, 360.0; found 361.0 [M+H]⁺. HPLC purity98.0%.

Example 27 N-hydroxy-3-(((2-phenylcyclopropyl)amino)methyl)benzamide TFA

The compound was synthesized using the I-27 following the procedure forExample 2. ¹HNMR (400 MHz, DMSO-d₆): δ 11.09 (bs, 1H), 8.95 (bs, 1H),7.72 (s, 1H), 7.57 (d, 1H, J=7.2 Hz), 7.42 (d, 1H, J=7.6 Hz), 7.33 (t,1H, J=7.6 Hz), 7.18 (t, 2H, J=7.6 Hz), 7.08 (t, 1H, J=7.6 Hz), 7.0 (d,2H, J=7.2 Hz), 3.79 (s, 2H), 2.92-2.81 (m, 1H), 2.22-2.20 (m, 1H),1.86-1.78 (m, 1H), 1.02-0.97 (m, 1H), 0.93-0.84 (m, 1H). LC-MS m/z calcdfor C₁₇H₁₈N₂O₂ 282.1; found 283.2 [M+H]⁺. HPLC purity 99.8%.

Example 28 N-hydroxy-4-(((2-phenylcyclopropyl)amino)methyl)benzamide TFASalt

The compound was synthesized using the I-28 following the procedure forExample 2. ¹HNMR (400 MHz, DMSO-d₆): δ 9.20 (bs, 2H), 7.65 (d, 2H, J=7.6Hz), 7.25 (d, 2H, J=7.2 Hz), 7.18 (t, 2H, J=7.6 Hz), 7.07 (t, 2H, J=7.2Hz), 6.80 (d, 2H, J=7.6 Hz), 3.75 (s, 2H), 2.88-2.75 (m, 1H), 2.23-2.15(m, 1H), 1.85-1.75 (m, 1H), 0.98-0.85 (m, 1H). LC-MS m/z calcd forC₁₇H₁₈N₂O₂ 282.1; found 283.2 [M+H]⁺. HPLC purity 99.5%.

Example 29 N-hydroxy-6-((2-phenylcyclopropyl)amino)hexanamide TFA Salt

The compound was synthesized using the I-29 following the procedure forExample 2. ¹HNMR (400 MHz, DMSO-d₆): δ 10.31 (bs, 1H), 8.77 (bs, 2H),7.32-7.25 (m, 2H), 7.23-7.14 (m, 3H), 3.09-3.00 (m, 2H), 2.98-2.91 (m,1H), 2.42-2.33 (m, 1H), 1.98-1.91 (m, 2H), 1.62-1.38 (m, 5H), 1.32-1.25(m, 3H). LC-MS m/z calcd for C₁₅H₂₂N₂O₂, 263.3; found 263.2 [M+H]⁺. HPLCpurity 96.4%.

Example 304-(3-((2-(4-fluorophenyl)cyclopropyl)amino)propyl)-N-hydroxybenzamideTFA Salt

The compound was synthesized using the I-30 following the procedure forExample 2. ¹HNMR (400 MHz, DMSO-d₆): δ 11.12 (s, 1H), 8.94 (bs, 2H),7.68 (d, 2H, J=8.0 Hz), 7.27 (d, 2H, J=8.0 Hz), 7.20-7.08 (m, 4H),3.09-3.01 (m, 2H), 2.98-2.91 (m, 1H), 2.72-2.63 (m, 2H), 2.47-2.37 (m,1H), 1.94-1.86 (m, 2H), 1.43-1.38 (m, 1H), 1.28-1.21 (m, 1H). LC-MS m/zcalcd for C₁₉H₂₁FN₂O₂, 328.1; found 329.4 [M+H]⁺. HPLC purity 96.6%.

Example 31N-(6-Hydroxycarbamoyl-hexyl)-4-[(2-phenyl-cyclopropylamino)-methyl]-benzamideTFA Salt

The compound was synthesized using the I-31 following the procedure forExample 2. ¹HNMR (400 MHz, DMSO-d₆): δ 10.29 (bs, 1H), 8.63 (bs, 1H),8.32 (t, 1H, J=5.2 Hz), 7.74 (d, 2H, J=8 Hz), 7.35 (d, 2H, J=8 Hz),7.20-7.16 (m, 2H), 7.09-7.06 (m, 2H), 6.85 (d, 2H, J=7.6 Hz), 3.79 (s,2H), 3.34-3.19 (m, 2H), 2.91 (bs, 1H), 2.25-2.17 (m, 1H), 1.92 (t, 1H,J=7.2 Hz), 1.84-1.80 (m, 1H), 1.55-1.42 (m, 4H), 1.32-1.20 (m, 4H),1.02-0.97 (m, 1H), 0.94-0.89 (m, 1H). LC-MS m/z calcd for C₂₄H₃₁N₃O₃,409.2; found 410.3 [M+H]⁺. HPLC purity 97.0%.

Example 324-(((2-(4-fluorophenyl)cyclopropyl)amino)methyl)-N-(7-(hydroxyamino)-7-oxoheptyl)benzamideTFA Salt

The compound was synthesized using the I-32 following the procedure forExample 2. ¹HNMR (400 MHz, DMSO-d₆): δ 10.30 (bs, 1H), 9.39 (bs, 2H),8.46-8.44 (m, 1H), 7.86 (d, 2H, J=8.4 Hz), 7.55 (d, 2H, J=8 Hz),7.19-7.09 (m, 4H), 4.36 (s, 2H), 3.26-3.21 (m, 2H), 2.93-1.88 (m, 1H),2.44-2.43 (m, 1H), 1.95-1.91 (m, 2H), 1.52-1.41 (m, 5H), 1.31-1.24 (m,5H). LC-MS m/z calcd for C₂₄H₃₀FN₃O₃, 427.2; found 428.5 [M+H]⁺. HPLCpurity 98.6%.

Example 33 4-(2-Phenyl-cyclopropylamino)-cyclohexanecarboxylic AcidHydroxyamide TFA Salt

The compound was synthesized using the I-33 following the procedure forExample 2. ¹HNMR (400 MHz, DMSO-d₆): δ 10.26 (bs, 1H), 8.54 (bs, 1H),7.21 (t, 2H, J=7.2 Hz), 7.09 (t, 1H, J=7.2 Hz), 7.00 (d, 2H, J=7.6 Hz),2.82 (s, 1H), 2.09 (s, 1H), 2.01-1.97 (m, 1H), 1.84-1.59 (m, 5H),1.50-1.26 (m, 5H), 1.01-0.92 (m, 2H). LC-MS m/z calcd C₁₆H₂₂N₂O₂[M+H]⁺275.1. found 275.1. HPLC purity 95%.

Example 34(1S,4R)—N-hydroxy-4-((1S)-1-((2-phenylcyclopropyl)amino)ethyl)cyclohexanecarboxamideTFA Salt

The compound was synthesized using the I-34 following the procedure forExample 2. ¹HNMR (400 MHz, DMSO-d₆): δ 10.34 (bs, 1H), 8.76 (bs, 1H),8.59 (bs, 1H), 7.33-7.27 (m, 2H), 7.24-7.22 (m, 1H), 7.20-7.17 (m, 2H),3.32-3.23 (m, 1H), 3.00-2.91 (m, 1H), 2.44-2.31 (m, 2H), 1.97-1.89 (m,1H), 1.72-1.65 (m, 5H), 1.43-1.29 (m, 5H), 1.19-1.00 (m, 3H). LC-MS m/zcalcd for C₁₈H₂₆N₂O₂, 302.2; found 303.2 [M+H]⁺. HPLC purity 99.1%.

Example 35N-hydroxy-4-((4-(((2-(4-(1-methyl-6-oxo-1,6-dihydropyridin-3-yl)phenyl)cyclopropyl)amino)methyl)piperidin-1-yl)methyl)benzamideTFA Salt

The compound was synthesized using the I-35 following the procedure forExample 2. ¹HNMR (400 MHz, DMSO-d₆): δ 11.29 (bs, 1H), 9.57 (bs, 1H),9.00 (bs, 2H), 8.08 (s, 1H), 7.83 (d, J=8.0 Hz, 2H), 7.79-7.76 (m, 1H),7.55 (d, J=8.0 Hz, 2H), 7.52-7.46 (m, 2H), 7.21 (d, J=8.0 Hz, 2H), 6.46(d, J=9.2 Hz, 1H), 4.31 (s, 2H), 3.49 (s, 3H), 3.44-3.34 (m, 2H),3.25-3.10 (m, 1H), 3.05-2.85 (m, 5H), 2.02-1.80 (m, 3H), 1.51-1.27 (m,4H). LC-MS m/z calcd for C₂₉H₃₄FN₄O₃, 486.3; found 487.6 [M+H]⁺. HPLCpurity 99.7%.

Example 36N-Hydroxy-4-{4-[(2-phenyl-cyclopropylamino)-methyl]-piperidin-1-ylmethyl}-benzamideTFA Salt

The compound was synthesized using the I-36 following the procedure forExample 2. ¹HNMR (400 MHz, DMSO-d₆): δ 10.80 (bs, 1H), 8.95 (bs, 1H),7.68 (d, 2H, J=8 Hz), 7.33 (d, 2H, J=8 Hz), 7.24-7.17 (m, 2H), 7.12-7.06(m, 1H), 7.03-6.98 (m, 2H), 3.45 (s, 2H), 2.78-2.72 (m, 2H), 2.46-2.42(m, 3H), 2.19-2.14 (m, 1H), 1.92-1.84 (m, 2H), 1.78-1.71 (m, 1H),1.68-1.59 (m, 2H), 1.39-1.30 (m, 1H), 1.16-1.04 (m, 2H), 0.81-0.62 (m,2H). LC-MS m/z calcd for C₂₃H₂₉N₃O₂, 379.2; found 380.2 [M+H]⁺. HPLCpurity 99.8%.

Example 374-((4-(((2-(4-(3,5-dimethylisoxazol-4-yl)phenyl)cyclopropyl)amino)methyl)piperidin-1-yl)methyl)-N-hydroxybenzamideTFA salt

The compound was synthesized using the I-37 following the procedure forExample 2. ¹HNMR (400 MHz, DMSO-d₆): δ 11.28 (bs, 1H), 9.53 (bs, 1H),9.04-8.84 (bs, 2H), 7.83 (d, J=7.2 Hz, 2H), 7.55 (d, J=7.2 Hz, 2H),7.32-7.24 (m, 4H), 4.32 (s, 2H), 3.50-3.37 (m, 2H), 3.06-2.92 (m, 5H),2.35 (s, 3H), 2.18 (s, 3H), 1.98-1.83 (m, 4H), 1.50-1.32 (m, 4H). LC-MSm/z calcd for C₂₈H₃₄N₄O₃, 474.3; found 475.3 [M+H]⁺. HPLC purity 99.9%.

Example 38N-hydroxy-4-((4-(((2-(4-(pyrimidin-5-yl)phenyl)cyclopropyl)amino)methyl)piperidin-1-yl)methyl)benzamideTFA Salt

The compound was synthesized using the I-38 following the procedure forExample 2. ¹HNMR (400 MHz, DMSO-d₆): δ 11.27 (bs, 1H), 9.70 (bs, 1H),9.16 (s, 1H), 9.11 (s, 2H), 9.06 (bs, 1H), 7.82 (d, 2H, J=8.4 Hz), 7.75(d, 2H, J=8 Hz), 7.55 (d, 2H, J=8 Hz), 7.33 (d, 2H, J=8 Hz), 4.32 (s,2H), 3.41-3.37 (m, 2H), 3.07-2.92 (m, 5H), 2.00-1.92 (m, 4H), 1.55-1.49(m, 1H), 1.47-1.33 (m, 3H). LC-MS m/z calcd for C₂₇H₃₁N₅O₂, 457.2; found458.6[M+H]⁺. HPLC purity 99.0%.

Example 396-((4-(((2-(4-(3,5-dimethylisoxazol-4-yl)phenyl)cyclopropyl)amino)methyl)piperidin-1-yl)methyl)-N-hydroxynicotinamideTFA Salt

The compound was synthesized using the I-39 following the procedure forExample 2. ¹HNMR (400 MHz, DMSO-d₆): δ 11.45 (bs, 1H), 9.97 (bs, 1H),9.05 (bs, 2H), 9.00-8.93 (m, 1H), 8.22 (d, 1H, J=7.2 Hz), 7.60 (d, 1H,J=8.4 Hz, 7.33-7.24 (m, 4H), 4.52-4.48 (m, 3H), 3.46-3.40 (m, 2H),3.11-3.01 (m, 5H), 2.36 (s, 3H), 2.18 (s, 3H), 1.98-1.91 (m, 3H),1.58-1.48 (m, 3H), 1.38-1.31 (m, 1H). LC-MS m/z calcd for C₂₇H₃₃N₅O₃,475.3. found 476.3 [M+H]⁺. HPLC purity 99.8%.

Example 40N-hydroxy-4-((4-(((2-phenylcyclopropyl)amino)methyl)-1H-pyrazol-1-yl)methyl)benzamideTFA Salt

The compound was synthesized using the I-40 following the procedure forExample 2. ¹HNMR (400 MHz, DMSO-d₆): δ 11.16 (bs, 1H), 9.01 (bs, 3H),7.87 (s, 1H), 7.69 (d, 2H, J=8 Hz), 7.54 (s, 1H), 7.32-7.24 (m, 4H),7.23-7.19 (m, 1H), 7.11 (d, 2H, J=7.2 Hz), 5.36 (s, 2H), 4.18 (s, 2H),2.92-2.85 (m, 1H), 2.40-2.31 (m, 1H), 1.42-1.36 (m, 1H), 1.32-1.23 (m,1H). LC-MS m/z calcd for C₂₁H₂₂N₄O₂, 362.4; found 363.4 [M+H]⁺. HPLCpurity 99.1%.

Example 41N-hydroxy-4-((4-(((2-phenylcyclopropyl)amino)methyl)-1H-1,2,3-triazol-1-yl)methyl)benzamideTFA Salt

The compound was synthesized using the I-41 following the procedure forExample 2. ¹HNMR (400 MHz, DMSO-d₆): δ 11.19 (bs, 1H), 9.39 (bs, 2H),9.03 (bs, 1H), 8.21 (s, 1H), 7.73 (d, 2H, J=7.6 Hz), 7.35 (d, 2H, J=8Hz), 7.32-7.24 (m, 2H), 7.22-7.16 (m, 1H), 7.12-7.08 (m, 2H), 5.68 (s,2H), 4.41 (s, 2H), 3.01-2.95 (m, 1H), 2.41-2.34 (m, 1H), 1.43-1.36 (m,1H), 1.32-1.22 (m, 1H). LC-MS m/z calcd for C₂₀H₂₁N₅O₂, 363.2; found364.2 [M+H]⁺. HPLC purity 99.8%.

Example 42N-hydroxy-4-(2-(4-(((2-phenylcyclopropyl)amino)methyl)piperidin-1-yl)ethyl)benzamideTFA Salt

The compound was synthesized using the I-42 following the procedure forExample 2. ¹HNMR (400 MHz, DMSO-d₆): δ 11.17 (bs, 1H), 9.69 (bs, 1H),9.11 (bs, 2H), 7.72 (d, 2H, J=7.6 Hz), 7.36-7.26 (m, 4H), 7.24-7.20 (m,1H), 7.15 (d, 2H, J=7.2 Hz), 3.70-3.55 (m, 2H), 3.40-3.15 (m, 3H),3.10-2.90 (m, 7H), 2.05-1.92 (m, 2H), 1.90-1.78 (m, 1H), 1.55-1.42 (m,3H), 1.35-1.25 (m, 1H). LC-MS m/z calcd for C₂₄H₃₁N₃O₂, 393.5; found394.5 [M+H]⁺. HPLC purity 97%

Example 43N-hydroxy-4-(3-(4-(((2-phenylcyclopropyl)amino)methyl)piperidin-1-yl)propyl)benzamideTFA Salt

The compound was synthesized using the I-43 following the procedure forExample 2. ¹HNMR (400 MHz, DMSO-d₆): δ 7.66 (d, 2H, J=8.4 Hz), 7.30-7.26(t, 4H, J=7.6 Hz), 7.22-7.20 (t, 1H, J=6.8 Hz), 7.15 (d, 2H, J=7.6 Hz),3.53 (m, 2H), 3.15-2.97 (m, 4H), 2.97-2.92 (m, 1H), 2.92-2.80 (m, 2H),2.69-2.60 (m, 2H), 2.45-2.38 (m, 1H), 2.00-1.88 (m, 5H), 1.46-1.35 (m,3H), 1.30-1.22 (m, 1H). LC-MS m/z calcd for C₂₅H₃₃N₃O₂, 407.2; found408.3 [M+H]⁺. HPLC purity 99%.

Example 44N-hydroxy-4-(3-(4-((2-phenylcyclopropyl)amino)piperidin-1-yl)propyl)benzamideTFA Salt

The compound was synthesized using the I-44 following the procedure forExample 2. ¹HNMR (400 MHz, DMSO-d₆): δ 11.13 (bs, 1H), 9.45 (bs, 1H),9.26 (bs, 2H), 7.69 (d, 2H, J=7.6 Hz), 7.33-7.26 (m, 4H), 7.23-7.21 (m,1H), 7.19-7.15 (m, 2H), 3.62-3.54 (m, 3H), 3.50-3.41 (m, 2H), 3.35-3.28(m, 1H), 3.06-2.91 (m, 5H), 2.70-2.61 (m, 1H), 2.25-2.18 (m, 2H),1.96-1.91 (m, 2H), 1.83-1.72 (m, 1H), 1.48-1.41 (m, 1H), 1.34-1.30 (m,1H). LC-MS m/z calcd for C₂₄H₃₁N₃O₂, 393.2; found 394.2 [M+H]⁺. HPLCpurity 99.6%.

Example 45 N-hydroxy-4-(3-(4-((methyl (2-phenylcyclopropyl)amino)methyl) piperidin-1-yl) propyl) benzamide TFA Salt

To a stirred solution of example 43 (0.05 g, 0.12 mmol) in methanol (5mL) was added paraformaldehyde (0.007 g, 0.24 mmol) and TEA (0.037 g,0.36 mmol) and continue stirred for 1 h at room temperature, sodiumborohydride (0.09 g, 0.245 mmol) were added and continue stirred for 30minute. Reaction mixture was quenched with water (20 mL) and extractedwith dichloromethane (2×20 mL). The organic portion was washed withwater, brine, dried over sodium sulphate and concentrated under reducedpressure to afford the crude product compound which was purified byreverse-phase HPLC using Chemsil C₁₈ (250 mm×4.6 mm×5mic) column with0.1% TFA in water:ACN to afford (0.02 g, 20%). ¹HNMR (400 MHz, DMSO-d₆):δ 11.16 (s, 1H), 9.35 (bs, 1H), 7.69 (d, J=8.4 Hz, 2H), 7.30-7.10 (m,7H), 3.53-3.50 (m, 3H), 3.28-2.76 (m, 10H), 2.67-2.63 (m, 3H), 2.04-1.83(m, 4H), 1.48-1.28 (m, 4H). LC-MS m/z calcd for C₂₆H₃₅N₃O₂, 421.3; found422.5 [M+H]⁺. HPLC purity 99.5%.

Example 46N-hydroxy-4-(3-(6-((2-phenylcyclopropyl)amino)-2-azaspiro[3.3]heptan-2-1)propyl)benzamideTFA Salt

The compound was synthesized using the I-46 following the procedure forExample 48. ¹HNMR (400 MHz, DMSO-d₆): δ 11.12 (bs, 1H), 9.97 (bs, 1H),9.35 (bs, 1H), 9.26 (bs, 1H), 7.68 (d, 2H, J=8 Hz), 7.32-7.24 (m, 4H),7.23-7.19 (m, 1H), 7.14 (d, 2H, J=7.2 Hz), 4.25-4.19 (m, 2H), 4.14-3.98(m, 3H), 3.82-3.73 (m, 2H), 3.14-3.02 (m, 2H), 2.89-2.78 (m, 1H),2.69-2.60 (m, 3H), 2.94-2.84 (m, 2H), 1.79-1.70 (m, 2H), 1.43-1.35 (m,1H), 1.30-1.26 (m, 1H). LC-MS m/z calcd for C₂₅H₃₁N₃O₂, 405.5; found406.5 [M+H]⁺. HPLC purity 99.5%.

Example 474-[3-(4-{[2-(4-Fluoro-phenyl)-cyclopropylamino]-methyl}-piperidin-1-yl)-propyl]-N-hydroxy-benzamideTFA Salt

The compound was synthesized using the I-47 following the procedure forExample 2. ¹HNMR (400 MHz, DMSO-d₆): δ 11.14 (bs, 1H), 9.27 (bs, 1H),8.96 (bs, 3H), 7.70 (d, 2H, J=8 Hz), 7.30 (d, 2H, J=8 Hz), 7.26-7.19 (m,2H), 7.16-7.10 (m, 2H), 3.58-3.46 (m, 2H), 3.08-2.98 (m, 4H), 2.96-2.82(m, 3H), 2.69-2.63 (m, 2H), 2.00-1.88 (m, 6H), 1.49-1.35 (m, 3H),1.31-1.24 (m, 1H). LC-MS m/z calcd for C₂₅H₃₂FN₃O₂, 425.3; found 426.5[M+H]⁺. HPLC purity 97.1%

Example 484-(3-(3-(((2-(4-fluorophenyl)cyclopropyl)amino)methyl)azetidin-1-yl)propyl)-N-hydroxybenzamide TFA Salt

To a solution of hydroxylamine hydrochloride (0.38 g, 5.33 mmol) inmethanol was added a solution of potassium hydroxide (0.3 g, 5.33 mmol)in methanol at 5-10° C. and stirred at that temperature for 15 min. Theformed precipitate was filtered through cotton plug and the filtrate wasadded to a solution of ethyl4-(3-(3-((2,2,2-trifluoro-N-(2-(4-fluorophenyl)cyclopropyl)acetamido)methyl)azetidin-1-yl)propyl)benzoate(I-48, 0.15 g, 0.3 mmol) in methanol (4 mL) at room temperature.Potassium hydroxide (0.3 g, 5.33 mmol) was added and the resultingmixture was stirred at room temperature for 1 h. The solvent was removedand ice-water was added to the resulting residue. The pH of the aqueousportion was adjusted to 7.0 with 10% acetic acid solution. The crudeproduct was extracted with dichloromethane (30 mL×3). The combinedorganic layer was washed with water, brine, dried over sodium sulphateand concentrated under reduced pressure to get the crude product whichwas mixed with dichloromethane (5 mL) and trifluoroacetic acid (0.5 mL)was added at 0° C. The reaction mixture was stirred for 10 min at sametemperature. The reaction mixture was concentrated under vacuum to getcrude TFA salt of product which was purified by reverse-phase HPLC usingChemsil C₁₈ (250 mm×4.6 mm×5mic) column with 0.1% TFA in water:ACN toafford the pure product as colourless solid (0.04 g, 34% yield). LC-MSm/z calcd for C₂₃H₂₈FN₃O₂, 397.5; found 398.5 [M+H]⁺.

Example 494-(3-(4-(((2-(3-fluorophenyl)cyclopropyl)amino)methyl)piperidin-1-yl)propyl)-N-hydroxybenzamideTFA Salt

The compound was synthesized using the I-49 following the procedure forExample 2. ¹HNMR (400 MHz, DMSO-d₆): δ 11.14 (bs, 1H), 9.38 (bs, 1H),9.07 (bs, 3H), 7.69 (d, 2H, J=8 Hz), 7.36-7.28 (m, 3H), 7.04-7.00 (m,3H), 3.54-3.50 (m, 2H), 3.28-3.17 (m, 1H), 3.10-2.98 (m, 5H), 2.93-2.82(m, 2H), 2.70-2.61 (m, 2H), 2.00-1.85 (m, 5H), 1.53-1.30 (m, 3H). LC-MSm/z calcd for C₂₅H₃₂FN₃O₂, 425.3; found 426.5 [M+H]⁺. HPLC purity 99.4%.

Example 504-(3-(4-(((2-(3,4-difluorophenyl)cyclopropyl)amino)methyl)piperidin-1-yl)propyl)-N-hydroxybenzamideTFA Salt

The compound was synthesized using the I-50 following the procedure forExample 2. ¹HNMR (400 MHz, DMSO-d₆): δ 11.14 (bs, 1H), 9.06 (bs, 1H),8.94 (bs, 1H), 7.70 (d, 2H, J=8 Hz), 7.40-7.24 (m, 4H), 7.09-7.03 (m,1H), 3.58-3.48 (m, 3H), 3.30-3.12 (m, 1H), 3.08-2.97 (m, 5H), 2.93-2.82(m, 2H), 2.69-2.64 (m, 2H), 1.98-1.86 (m, 5H), 1.48-1.30 (m, 3H). LC-MSm/z calcd for C₂₅H₃₁F₂N₃O₂, 443.2. found 444.5 [M+H]⁺.

HPLC purity 99.6%.

Example 51N-hydroxy-4-(3-(4-(((2-(4-methoxyphenyl)cyclopropyl)amino)methyl)piperidin-1-yl)propyl)benzamideTFA Salt

The compound was synthesized using the I-51 following the procedure forExample 2. ¹HNMR (400 MHz, DMSO-d₆): δ 11.13 (bs, 1H), 9.35 (bs, 1H),8.98 (bs, 1H), 7.69 (d, 2H, J=7.6 Hz), 7.29 (d, 2H, J=8.4 Hz), 7.08 (d,2H, J=8.4 Hz), 6.84 (d, 2H, J=8.4 Hz), 3.70 (s, 3H), 3.53-3.50 (m, 2H),3.07-3.01 (m, 4H), 2.91-2.86 (m, 3H), 2.67-2.53 (m, 3H), 2.00-1.92 (m,5H), 1.40-1.38 (m, 3H), 1.22-1.17 (m, 1H). LC-MS m/z calcd forC₂₆H₃₅N₃O₃ [M+H]⁺ 438.2. found 438.3. HPLC purity 99.5%.

Example 524-(3-(4-(((2-(4-((4-fluorobenzyl)oxy)phenyl)cyclopropyl)amino)methyl)piperidin-1-yl)propyl)-N-hydroxybenzamideTFA Salt

The compound was synthesized using the I-52 following the procedure forExample 2. ¹HNMR (400 MHz, DMSO-d₆): δ 11.14 (bs, 1H), 9.10 (bs, 1H),8.96 (bs, 1H), 8.82 (bs, 2H), 7.71 (d, 2H, J=7.6 Hz), 7.48-7.42 (m, 2H),7.31 (d, 2H, J=8 Hz), 7.20 (t, 2H, J=8.8 Hz), 7.09 (d, 2H, J=8.4 Hz),6.93 (d, 2H, J=8.4 Hz), 5.01 (s, 2H), 3.58-3.50 (m, 2H), 3.06-2.97 (m,4H), 2.92-2.85 (m, 4H), 2.70-2.62 (m, 2H), 2.40-2.35 (m, 1H), 2.00-1.88(m, 5H), 1.45-1.34 (m, 3H). LC-MS m/z calcd for C₃₂H₃₈FN₃O₃, 531.3;found 532.4 [M+H]⁺. HPLC purity 99.9%.

Example 53N-hydroxy-4-(3-(4-(((2-(4-(morpholine-4-carbonyl)phenyl)cyclopropyl)amino)methyl)piperidin-1-yl)propyl)benzamideTFA Salt

The compound was synthesized using the I-54 following the procedure forExample 2. ¹HNMR (400 MHz, DMSO-d₆): δ 11.07 (bs, 1H), 9.41 (bs, 1H),9.27 (bs, 2H), 7.69 (d, 2H, J=8 Hz), 7.36-7.29 (m, 3H), 7.27-7.22 (m,3H), 3.65-3.45 (m, 7H), 3.41-3.25 (m, 3H), 3.10-2.98 (m, 5H), 2.96-2.85(m, 2H), 2.70-2.61 (m, 3H), 2.01-1.85 (m, 5H), 1.78-1.70 (m, 1H),1.52-1.48 (m, 1H), 1.45-1.31 (m, 2H). LC-MS m/z calcd for C₃₀H₄₀N₄O₄,520.3; found 521.3 [M+H]⁺; HPLC purity 99.6%.

Example 54N-hydroxy-4-(3-(4-(((2-(4-(piperidine-1-carbonyl)phenyl)cyclopropyl)amino)methyl)piperidin-1-yl)propyl)benzamideTFA Salt

The compound was synthesized using the I-55 following the procedure forExample 2. ¹HNMR (400 MHz, DMSO-d₆): δ 11.14 (bs, 1H), 9.31 (bs, 1H),9.15 (bs, 3H), 7.70 (d, 2H, J=8.4 Hz), 7.32-7.26 (m, 4H), 7.24-7.20 (m,2H), 3.56-3.50 (m, 6H), 3.27-3.26 (m, 2H), 3.05-2.85 (m, 5H), 2.93-2.83(m, 2H), 2.68-2.63 (m, 2H), 2.00-1.90 (m, 5H), 1.62-1.57 (m, 2H),1.53-1.32 (m, 7H). LC-MS m/z calcd for C₃₁H₄₂N₄O₃, 518.3. found 519.3[M+H]⁺. HPLC purity 99.4%.

Example 55N-(2-(dimethylamino)ethyl)-4-(2-(((1-(3-(4-(hydroxycarbamoyl)phenyl)propyl)piperidin-4-yl)methyl)amino)cyclopropyl)benzamideTFA Salt

The compound was synthesized using the I-53 following the procedure forExample 2. ¹HNMR (400 MHz, DMSO-d₆): δ 11.15 (bs, 1H), 9.51 (bs, 1H),9.43 (bs, 1H), 9.16 (bs, 2H), 8.65 (bs, 1H), 7.79 (d, 2H, J=8.4 Hz),7.69 (d, 1H, J=8.0 Hz), 7.62 (d, 1H, J=8.0 Hz), 7.30-7.23 (m, 4H),3.50-3.48 (m, 4H), 3.28-3.21 (m, 2H), 3.08-2.98 (m, 5H), 2.90-2.81 (m,8H), 2.69-2.60 (m, 3H), 2.00-1.82 (m, 5H), 1.57-1.50 (m, 1H), 1.46-1.30(m, 3H). LC-MS m/z calcd for C₃₀H₄₃N₅O₃, 521.3; found 522.2 [M+H]⁺. HPLCpurity 99.97%.

Example 564-(3-(4-(((2-(4′-chloro-[1,1′-biphenyl]-4-yl)cyclopropyl)amino)methyl)piperidin-1-yl)propyl)-N-hydroxybenzamideTFA Salt

The compound was synthesized using the I-56 following the procedure forExample 2. ¹HNMR (400 MHz, DMSO-d₆): δ 11.13 (bs, 1H), 9.39 (bs, 1H),9.08 (bs, 2H), 7.70-7.64 (m, 4H), 7.59 (d, 2H, J=8.4 Hz), 7.48 (d, 2H,J=8.4 Hz), 7.30-7.25 (m, 4H), 3.53-3.43 (m, 3H), 3.08-2.97 (m, 5H),2.89-2.86 (m, 2H), 2.68-2.65 (m, 2H), 2.01-1.90 (m, 5H), 1.52-1.32 (m,4H). LC-MS m/z calcd for C₃₁H₃₆ClN₃O₂, 518.2; found 518.2 [M+H]⁺. HPLCpurity 99.8%.

Example 574-(3-(4-(((2-(4′-fluoro-[1,1′-biphenyl]-4-yl)cyclopropyl)amino)methyl)piperidin-1-yl)propyl)-N-hydroxybenzamideTFA Salt

The compound was synthesized using the I-57 following the procedure forExample 2. ¹HNMR (400 MHz, DMSO-d₆): δ 11.13 (bs, 1H), 9.14 (bs, 1H),8.92 (bs, 2H), 7.75-7.64 (m, 4H), 7.57 (d, J=8.1 Hz, 2H), 7.35-7.20 (m,6H), 3.6-3.5 (m, 2H), 3.10-2.96 (m, 5H), 2.94-2.82 (m, 2H), 2.72-2.62(m, 3H), 2.02-1.86 (m, 5H), 1.54-1.44 (m, 1H), 1.44-1.28 (m, 3H). LC-MSm/z calcd for C₃₁H₃₆FN₃O₂, 501.3; found 502.3 [M+H]⁺. HPLC purity 99.7%.

Example 584-(3-(3-(((2-(4′-fluoro-[1,1′-biphenyl]-4-yl)cyclopropyl)amino)methyl)azetidin-1-yl)propyl)-N-hydroxybenzamide TFA Salt

The compound was synthesized using the I-58 following the procedure forExample 48. ¹HNMR (400 MHz, DMSO-d₆): δ 11.13 (bs, 1H), 10.05 (bs, 1H),9.17 (bs, 2H), 9.00 (bs, 1H), 7.70-7.64 (m, 4H), 7.57 (d, 2H, J=8.0 Hz),7.28-7.24 (m, 6H), 4.25-4.15 (m, 1H), 4.14-4.10 (m, 2H), 3.92-3.81 (m,2H), 3.48-3.31 (m, 2H), 3.11-3.07 (m, 3H), 2.65-2.61 (m, 2H), 2.48-2.43(m, 1H), 1.75-1.73 (m, 2H), 1.49-1.41 (m, 1H), 1.39-1.31 (m, 1H). LC-MSm/z calcd for C₂₉H₃₂FN₃O₂, 473.5; found 474.5 [M+H]⁺. HPLC purity 99.8%.

Example 594-(3-(4-(((2-(4′-cyano-[1,1′-biphenyl]-4-yl)cyclopropyl)amino)methyl)piperidin-1-yl)propyl)-N-hydroxybenzamideTFA Salt

The compound was synthesized using the I-59 following the procedure forExample 2. ¹HNMR (400 MHz, DMSO-d₆): δ 11.13 (bs, 1H), 9.12 (bs, 1H),8.92 (bs, 2H), 7.97-7.93 (m, 3H), 7.72-7.66 (m, 5H), 7.35-7.24 (m, 4H),3.70-3.45 (m, 4H), 3.18-2.98 (m, 4H), 3.30-3.16 (bs, 2H), 3.08-2.98 (bs,4H), 2.95-2.82 (m, 2H), 2.70-2.62 (m, 2H), 2.02-1.90 (m, 4H), 1.55-1.30(m, 3H). LC-MS m/z calcd for C₃₂H₃₆N₄O₂, 508.3; found 527.3[M+H+17]⁺.HPLC purity 99.8%.

Example 60N-hydroxy-4-(3-(4-(((2-(4-(1-methyl-2-oxo-1,2-dihydropyridin-4-yl)phenyl)cyclopropyl)amino)methyl)piperidin-1-yl)propyl)benzamideTFA Salt

The compound was synthesized using the I-60 following the procedure forExample 2. ¹HNMR (400 MHz, DMSO-d₆): δ 11.14 (bs, 1H), 9.21 (bs, 1H),8.95 (bs, 3H), 8.07 (s, 1H), 7.81-7.76 (m, 1H), 7.69 (d, J=8.0 Hz, 2H),7.50 (d, J=8.0 Hz, 2H), 7.30 (d, J=7.6 Hz, 2H), 7.21 (d, J=7.6 Hz, 2H),6.49 (d, J=9.6 Hz, 1H), 3.56-3.48 (m, 5H), 3.26-3.18 (m, 1H), 3.07-2.97(m, 5H), 2.92-2.82 (m, 2H), 2.69-2.63 (m, 3H), 2.02-1.94 (m, 5H),1.48-1.27 (m, 3H). LC-MS m/z calcd for C₃₁H₃₈N₄O₃, 514.3. found513.3[M−H]⁺. HPLC purity 99.3%.

Example 61N-hydroxy-4-(3-(4-(((2-(4-(pyrimidin-5-yl)phenyl)cyclopropyl)amino)methyl)piperidin-1-yl)propyl)benzamideTFA Salt

The compound was synthesized using the I-61 following the procedure forExample 2. ¹HNMR (400 MHz, DMSO-d₆): δ 11.14 (s, 1H), 9.24 (bs, 1H),9.16 (s, 1H), 9.11 (s, 2H), 8.98 (bs, 2H), 7.75 (d, J=8.4 Hz, 2H), 7.69(d, J=8.0 Hz, 2H), 7.34 (d, J=8.4 Hz, 2H), 7.29 (d, J=8.4 Hz, 1H), 3.52(d, J=11.6 Hz, 2H), 3.30-3.18 (m, 1H), 3.10-2.98 (m, 5H), 2.95-2.80 (m,2H), 2.70-2.62 (m, 1H), 2.55 (m, 1H), 2.20-1.70 (m, 5H), 1.58-1.48 (m,1H), 1.46-1.32 (m, 2H). LC-MS m/z calcd for C₂₉H₃₅N₅O₂, 485.2; found486.2 [M+H]⁺. HPLC purity 99.7%.

Example 62N-hydroxy-4-(3-(4-(((2-(4-(1-methyl-1H-pyrazol-4-yl)phenyl)cyclopropyl)amino)methyl)piperidin-1-yl)propyl) benzamide TFA Salt

The compound was synthesized using the I-62 following the procedure forExample 2. ¹HNMR (400 MHz, DMSO-d₆): 11.13 (s, 1H), 9.17 (s, 1H), 8.91(s, 2H), 8.07 (s, 1H), 7.80 (s, 1H), 7.70-7.62 (d, J=8 Hz, 2H),7.48-7.40 (d, J=8.4 Hz, 2H), 7.35-7.20 (d, J=8 Hz, 2H), 7.15-7.10 (d,J=8.4 Hz, 2H), 3.83 (s, 3H), 3.54-3.51 (m, 2H), 3.24-3.19 (m, 1H),3.02-2.95 (m, 4H), 2.89-2.86 (m, 3H), 2.66 (m, 2H), 2.48-2.30 (m, 1H),2.05-1.92 (m, 5H), 1.44-1.33 (m, 2H), 1.27-1.22 (m, 1H). LC-MS m/z calcdfor C₂₉H₃₇N₅O₂, 487.3; found 488.3[M+H]⁺. HPLC purity 99.8%.

Example 63N-hydroxy-4-(3-(3-(((2-(4-(1-methyl-1H-pyrazol-4-yl)phenyl)cyclopropyl)amino)methyl)azetidin-1-yl)propyl)benzamideTFA Salt

The compound was synthesized using the I-63 following the procedure forExample 48. ¹HNMR (400 MHz, DMSO-d₆): δ 11.13 (bs, 1H), 9.79 (bs, 1H),8.99 (bs, 2H), 8.08 (s, 1H), 7.81 (s, 1H), 7.69 (d, 2H, J=8.0 Hz), 7.47(d, 2H, J=8.4 Hz), 7.28-7.23 (m, 2H), 7.14 (d, 2H, J=8 Hz), 4.22-4.14(m, 1H), 4.11-3.95 (m, 2H), 3.89-3.83 (m, 1H), 3.83 (s, 3H), 3.29-3.01(m, 5H), 2.92-2.87 (m, 1H), 2.68-2.60 (m, 1H), 2.41-2.30 (m, 2H),1.70-1.62 (m, 2H), 1.42-1.35 (m, 1H), 1.34-1.26 (m, 1H). LC-MS m/z calcdfor C₂₇H₃₃N₅O₂, 459.6; found 460.6 [M+H]⁺. HPLC purity 99%.

Example 644-(3-(4-(((2-(4-(3,5-dimethylisoxazol-4-yl)phenyl)cyclopropyl)amino)methyl)piperidin-1-yl)propyl)-N-hydroxybenzamideTFA Salt

The compound was synthesized using the I-64 following the procedure forExample 2. ¹HNMR (400 MHz, DMSO-d₆): δ11.13 (bs, 1H), 9.14 (bs, 1H),8.92 (bs, 2H), 7.69 (d, 2H, J=7.6 Hz), 7.32-7.28 (m, 6H), 3.54-3.51 (m,2H), 3.26-3.20 (m, 1H), 3.08-2.98 (m, 5H), 2.92-2.85 (m, 2H), 2.68-2.64(m, 2H), 2.35 (s, 3H), 2.18 (s, 3H), 2.01-1.90 (m, 4H), 1.78-1.64 (m,1H), 1.51-1.47 (m, 1H), 1.40-1.32 (m, 3H). LC-MS m/z calcd forC₃₀H₃₈N₄O₃, 502.3; found 503.3[M+H]⁺. HPLC purity 99.5%.

Example 653-(3-(3-(((2-(4-(3,5-dimethylisoxazol-4-yl)phenyl)cyclopropyl)amino)methyl)azetidin-1-yl)propyl)-N-hydroxybenzamideTFA Salt

The compound was synthesized using the I-65 following the procedure forExample 48. ¹HNMR (400 MHz, DMSO-d₆): δ 11.13 (bs, 1H), 9.81 (bs, 1H),8.97 (bs, 3H), 7.69 (d, 2H, J=8.0 Hz), 7.33-7.26 (m, 6H), 4.21-4.18 (m,1H), 4.12-4.00 (m, 2H), 3.89-3.80 (m, 2H), 3.40-3.32 (m, 2H), 3.29-2.98(m, 5H), 2.64-2.60 (m, 1H), 2.36 (s, 3H), 2.18 (s, 3H), 1.80-1.73 (m,2H), 1.44-1.41 (m, 1H), 1.39-1.31 (m, 1H). LC-MS m/z calcd forC₂₈H₃₄N₄O₃, 474.6; found 475.6 [M+H]⁺. HPLC purity 99%.

Example 66N-hydroxy-4-(3-(4-(((2-(4-(6-(trifluoromethyl)pyridin-3-yl)phenyl)cyclopropyl)amino)methyl)piperidin-1-yl)propyl)benzamideTFA Salt

The compound was synthesized using the I-66 following the procedure forExample 2. ¹HNMR (400 MHz, DMSO-d₆): δ 11.14 (bs, 1H), 9.18 (bs, 1H),9.07 (s, 1H), 8.99 (bs, 2H), 8.33 (d, 1H, J=8 Hz), 7.96 (d, 1H, J=8.4Hz), 7.77 (d, 2H, J=8 Hz), 7.70 (d, 1H, J=8 Hz), 7.62 (d, 1H, J=7.6 Hz),7.35 (d, 2H, J=8 Hz), 7.30 (d, 1H, J=8 Hz), 7.25 (d, 1H, J=8 Hz),3.55-3.48 (m, 2H), 3.30-3.16 (m, 1H), 3.10-2.84 (m, 2H), 2.69-2.61 (m,2H), 2.01-1.86 (m, 5H), 1.56-1.50 (m, 1H), 1.45-1.32 (m, 3H). LC-MS m/zcalcd for C₃₁H₃₅F₃N₄O₂, 552.3; found 553.3 [M+H]⁺. HPLC purity 99.1%.

Example 67N-hydroxy-4-(3-(4-(((2-(1-isopropyl-1H-pyrazol-4-yl)cyclopropyl)amino)methyl)piperidin-1-yl)propyl)benzamideTFA Salt

The compound was synthesized using the I-67 following the procedure forExample 2. ¹HNMR (400 MHz, DMSO-d₆): δ 11.14 (bs, 1H), 9.10 (bs, 1H),8.78 (bs, 2H), 7.70 (d, 2H, J=8 Hz), 7.61 (s, 1H), 7.31-7.28 (m, 3H),4.40-4.36 (m, 1H), 3.54-3.50 (m, 2H), 3.30-3.11 (m, 1H), 3.07-2.98 (m,4H), 2.92-2.76 (m, 4H), 2.24-1.98 (m, 2H), 1.97-1.90 (m, 5H) 1.41-1.30(m, 8H), 1.10-1.05 (m, 1H). LC-MS m/z calcd for C₂₅H₃₇N₅O₂, 439.6; found440.6 [M+H]⁺. HPLC purity 99.2%.

Example 68N-hydroxy-4-(3-(4-(((2-(1-phenyl-1H-pyrazol-4-yl)cyclopropyl)amino)methyl)piperidin-1-yl)propyl)benzamideTFA Salt

The compound was synthesized using the I-68 following the procedure forExample 2. ¹HNMR (400 MHz, DMSO-d₆): δ 11.14 (bs, 1H), 8.88 (bs, 3H),8.36 (s, 1H), 7.75-7.65 (m, 5H), 7.49-7.45 (m, 2H), 7.31-7.26 (m, 3H),3.55-3.51 (m, 2H), 3.08-2.98 (m, 4H), 2.95-2.84 (m, 3H), 2.71-2.63 (m,2H), 2.00-1.89 (m, 6H), 1.45-1.34 (m, 3H), 1.25-1.19 (m, 1H). LC-MS m/zcalcd for C₂₈H₃₅N₅O₂, 473.3; found 474.3 [M+H]⁺. HPLC purity 99.5%.

Example 69N-hydroxy-4-(3-(4-(((2-(2-methylthiazol-5-yl)cyclopropyl)amino)methyl)piperidin-1-yl)propyl)benzamideTFA Salt

The compound was synthesized using the I-69 following the procedure forExample 2. ¹HNMR (400 MHz, DMSO-d₆): δ 11.10 (bs, 1H), 9.36 (bs, 1H),9.10 (bs, 2H), 7.69 (d, 2H, J=8.4 Hz), 7.42 (s, 1H), 7.29 (d, 2H, J=7.6Hz), 3.56-3.48 (m, 2H), 3.30-3.16 (m, 1H), 3.06-2.96 (m, 4H), 2.94-2.82(m, 2H), 2.70-2.64 (m, 2H), 2.62-2.58 (m, 1H), 2.58 (s, 3H), 2.00-1.86(m, 5H) 1.56-1.46 (m, 1H), 1.42-1.32 (m, 2H), 1.32-1.26 (m, 1H). LC-MSm/z calcd for C₂₃H₃₂N₄O₂S, 428.5; found 429.5 [M+H]⁺.

Example 70N-hydroxy-4-(3-(4-(((2-(pyridin-3-yl)cyclopropyl)amino)methyl)piperidin-1-yl)propyl)benzamideTFA Salt

The compound was synthesized using the I-70 following the procedure forExample 2. ¹HNMR (400 MHz, DMSO-d₆): δ 11.13 (bs, 1H), 9.35 (bs, 1H),9.11 (bs, 2H), 8.57 (s, 1H), 8.51 (d, 1H, J=4.8 Hz), 7.75-7.67 (m, 3H),7.49-7.45 (m, 1H), 7.29 (d, 2H, J=8.4 Hz), 3.59-3.53 (m, 2H), 3.08-2.98(m, 5H), 2.94-2.82 (m, 2H), 2.73-2.67 (m, 2H), 2.02-1.91 (m, 5H),1.78-1.71 (m, 1H), 1.55-1.51 (m, 1H), 1.45-1.38 (m, 3H). LC-MS m/z calcdfor C₂₄H₃₂N₄O₂, 408.3; found 409.3 [M+H]⁺.

Example 71N-hydroxy-4-(3-(2-(((2-(4-methoxyphenyl)cyclopropyl)amino)methyl)-5,6-dihydroimidazo[1,2-a]pyrazin-7(8H)-yl)propyl)benzamideTFA Salt

The compound was synthesized using the I-71 following the procedure forExample 2. ¹HNMR (400 MHz, DMSO-d₆): δ 11.18 (bs, 1H), 9.31 (bs, 2H),7.69 (d, 2H, J=7.6 Hz), 7.31-7.27 (m, 3H), 7.02 (d, 2H, J=9.2 Hz), 6.83(d, 2H, J=8.4 Hz), 4.40-4.29 (m, 2H), 4.23-4.11 (m, 4H), 3.69 (s, 3H),3.60-3.50 (m, 2H) 3.16-3.08 (m, 2H), 2.88-2.76 (m, 1H) 2.71-2.65 (m,2H), 2.32-2.24 (m, 1H), 2.08-1.98 (m, 2H), 1.36-1.31 (m, 1H), 1.22-1.14(m, 1H). LC-MS m/z calcd for C₂₇H₃₃N₅O₃, 475.3; found 474.5 [M−H]⁺. HPLCpurity 99.2%.

Example 724-(3-(2-(((2-(4-fluorophenyl)cyclopropyl)amino)methyl)-5,6-dihydroimidazo[1,2-a]pyrazin-7(8H)-yl)propyl)-N-hydroxybenzamideTFA Salt

The compound was synthesized using the I-72 following the procedure forExample 2. ¹HNMR (400 MHz, DMSO-d₆): δ 11.12 (s, 1H), 9.27 (bs, 2H),7.68 (d, 2H, J=8.0 Hz), 7.29 (d, 2H, J=7.6 Hz), 7.24 (s, 1H), 7.13-7.07(m, 4H), 4.16-4.12 (m, 2H), 3.89 (bs, 4H), 3.38-3.31 (m, 2H), 2.85 (s,1H), 2.67 (t, 2H, J=7.2 Hz), 2.31 (d, 1H, J=6.0 Hz), 1.96 (bs, 2H), 1.37(t, 1H, J=4.4 Hz), 1.24 (s, 1H), 1.21 (s, 2H). LC-MS m/z calcd forC₂₆H₃₀FN₅O₂, 463.2; found 464.3 [M+H]⁺. HPLC purity 99.6%.

Example 734-(3-(4-(((2-(3,4-difluorophenyl)cyclopropyl)amino)methyl)-1H-imidazol-1-yl)propyl)-N-hydroxybenzamideTFA Salt

The compound was synthesized using the I-73 following the procedure forExample 2. ¹HNMR (400 MHz, DMSO-d₆): δ 11.12 (bs, 1H), 9.20 (bs, 2H),8.05 (s, 1H), 7.67 (d, 1H, J=8.0 Hz), 7.60 (d, 1H, J=7.6 Hz), 7.38-7.17(m, 5H), 7.00-6.96 (m, 1H), 4.19 (s, 2H), 4.05-3.92 (m, 2H), 2.93-2.89(m, 1H), 2.58-2.50 (m, 2H), 2.35-2.30 (m, 1H), 2.07-1.98 (m, 2H),1.43-1.34 (m, 1H), 1.32-1.24 (m, 1H). LC-MS m/z calcd for C₂₃H₂₄F₂N₄O₂,426.2; found 427.2 [M+H]⁺. HPLC purity 99.4%.

Example 74N-hydroxy-4-(3-(4-(((2-phenylcyclopropyl)amino)methyl)-1H-imidazol-1-yl)propyl)benzamideTFA Salt

The compound was synthesized using the I-74 following the procedure forExample 2. ¹HNMR (400 MHz, DMSO-d₆): δ 11.13 (bs, 1H), 8.99 (s, 1H),7.68 (d, 2H, J=8.0 Hz), 7.57 (s, 1H), 7.31-7.24 (m, 4H), 7.22-7.18 (m,1H), 7.08 (d, 2H, J=7.6 Hz), 4.37 (s, 2H), 4.20-4.16 (m, 2H), 2.92-2.85(m, 1H), 2.68-2.60 (m, 2H), 2.28-2.21 (m, 1H), 2.12-2.04 (m, 2H),1.38-1.30 (m, 1H), 1.25-1.18 (m, 1H). LC-MS m/z calcd for C₂₃H₂₆N₄O₂,390.2; found 391.2 [M+H]⁺. HPLC purity 99.0%.

Example 75N-hydroxy-4-(3-(4-(((2-phenylcyclopropyl)amino)methyl)-1H-imidazol-1-yl)propyl)benzamide TFA Salt

The compound was synthesized using the I-75 following the procedure forExample 2. ¹HNMR (400 MHz, DMSO-d₆): δ 11.14 (bs, 1H), 9.20 (bs, 2H),8.31 (s, 1H), 7.67 (d, 2H, J=7.6 Hz), 7.46 (s, 1H), 7.27-7.23 (m, 4H),7.19-7.15 (m, 1H), 7.08 (d, 2H, J=7.2 Hz), 4.30-4.23 (m, 2H), 4.08-4.00(m, 2H), 2.94-2.90 (m, 1H), 2.59-2.55 (m, 2H), 2.36-2.31 (m, 1H),2.05-1.98 (m, 2H), 1.42-1.36 (m, 1H) 1.27-1.22 (m, 1H). LC-MS m/z calcdfor C₂₃H₂₆N₄O₂, 390.2; found 391.2 [M+H]⁺. HPLC purity 99.7%.

Example 76N-hydroxy-4-(3-(4-(((2-phenylcyclopropyl)amino)methyl)-1H-pyrazol-1-yl)propyl)benzamideTFA Salt

The compound was synthesized using the I-76 following the procedure forExample 2. ¹HNMR (400 MHz, DMSO-d₆): δ 11.11 (bs, 1H), 9.03 (bs, 3H),7.77 (s, 1H), 7.67 (d, 2H, J=8.4 Hz), 7.52 (s, 1H), 7.29-7.16 (m, 5H),7.12 (d, 2H, J=7.6 Hz), 4.20-4.17 (m, 2H), 4.07 (t, 2H, J=6.8 Hz),2.93-2.87 (m, 1H), 2.65-2.53 (m, 2H), 2.37-2.32 (m, 1H), 2.06-1.99 (m,2H), 1.43-1.37 (m, 1H) 1.31-1.26 (m, 1H). LC-MS m/z calcd forC₂₃H₂₆N₄O₂, 390.2; found 391.2 [M+H]⁺. HPLC purity 99.7%.

Example 77N-hydroxy-4-(3-(4-(((2-phenylcyclopropyl)amino)methyl)-1H-1,2,3-triazol-1-yl)propyl)benzamideTFA Salt

The compound was synthesized using the I-77 following the procedure forExample 2. ¹HNMR (400 MHz, DMSO-d₆): δ 11.12 (bs, 1H), 9.44 (bs, 2H),8.99 (bs, 1H), 8.16 (s, 1H), 7.68 (d, 2H, J=8.4 Hz), 7.30-7.24 (m, 4H),7.20-7.16 (m, 1H), 7.11-7.09 (m, 2H), 4.45 (s, 2H), 4.42-4.36 (m, 2H),2.98-2.95 (m, 1H), 2.60-2.53 (m, 2H), 2.38-2.33 (m, 1H), 2.13-2.05 (m,2H), 1.43-1.38 (m, 1H) 1.29-1.24 (m, 1H). LC-MS m/z calcd forC₂₂H₂₅N₅O₂, 391.4; found 392.4 [M+H]⁺. HPLC purity 99.6%.

Example 784-(3-(6-(((2-(4-fluorophenyl)cyclopropyl)amino)methyl)-3,4-dihydroisoquinolin-2(1H)-yl)propyl)-N-hydroxybenzamideTFA Salt

The compound was synthesized using the I-78 following the procedure forExample 2. ¹HNMR (400 MHz, DMSO-d₆): δ 11.14 (bs, 1H), 9.91 (bs, 1H),9.37 (bs, 1H), 9.21 (bs, 1H), 8.95 (bs, 1H), 7.73-7.68 (m, 2H),7.39-7.28 (m, 4H), 7.24-7.18 (m, 1H), 7.16-7.08 (m, 4H), 4.96-4.77 (m,1H), 4.32-4.22 (m, 1H), 4.05-3.94 (m, 1H), 3.92-3.84 (m, 1H), 3.78-3.66(m, 1H), 3.35-3.28 (m, 2H), 3.26-3.27 (m, 2H), 3.07-2.93 (m, 1H),2.90-2.81 (m, 1H), 2.78-2.68 (m, 2H), 2.28-2.21 (m, 1H), 2.10-2.03 (m,1H), 1.45-1.36 (m, 1H), 1.32-1.26 (m, 2H). LC-MS m/z calcd forC₂₉H₃₂FN₃O₂, 473.2; found 474.2 [M+H]⁺. HPLC purity 96.9%.

Example 794-((7-(((2-(4-fluorophenyl)cyclopropyl)amino)methyl)-3,4-dihydroisoquinolin-2(1H)-yl)methyl)-N-hydroxybenzamideTFA Salt

The compound was synthesized using the I-79 following the procedure forExample 2. ¹HNMR (400 MHz, DMSO-d₆): δ 11.28 (bs, 1H), 10.4 (bs, 1H),9.30 (bs, 1H), 9.19 (bs, 1H), 7.86-7.77 (m, 2H), 7.63-7.56 (m, 2H),7.37-7.32 (m, 1H), 7.27-7.20 (m, 2H), 7.11-7.09 (m, 4H), 4.56-4.46 (m,2H), 4.28-4.20 (m, 4H), 3.75-3.66 (m, 2H), 3.13-3.04 (m, 2H), 2.84-2.80(m, 1H), 2.34-2.30 (m, 1H), 1.41-1.34 (m, 1H), 1.31-1.23 (m, 1H). LC-MSm/z calcd for C₂₇H₂₈FN₃O₂, 445.2; found 446.1 [M+H]⁺. HPLC purity 97.0%.

Example 804-((2-(((2-(4-fluorophenyl)cyclopropyl)amino)methyl)-5,6-dihydroimidazo[1,2-a]pyrazin-7(8H)-yl)methyl)-N-hydroxybenzamideTFA Salt

The compound was synthesized using the I-80 following the procedure forExample 2. ¹HNMR (400 MHz, DMSO-d₆): δ 11.17 (s, 1H), 9.14 (bs, 1H),7.75-7.67 (m, 2H), 7.44-7.39 (m, 2H), 7.22-7.18 (m, 1H), 7.13-7.05 (m,4H), 4.21-3.71 (m, 8H), 3.09-2.97 (m, 1H), 2.96-2.89 (m, 1H), 2.86-2.81(m, 1H), 2.32-2.26 (m, 1H), 1.41-1.39 (m, 1H), 1.26-1.19 (m, 2H). LC-MSm/z calcd for C₂₄H₂₆FN₅O₂, 436.1; found 436.2 [M+H]⁺. HPLC purity 99.8%.

Example 81N-hydroxy-4-(3-(4(((2-(1,3,3,-trimethyl-2-oxoindoline-5-yl)cyclopropyl)amino)methyl)piperidine-1-yl)propyl)benzamideTFA Salt

The compound was synthesized using the I-81 following the procedure forExample 2. ¹HNMR (400 MHz, DMSO-d₆): δ 11.16 (bs, 1H), 9.30 (bs, 1H),8.98 (bs, 3H), 7.69 (d, 2H, J=8 Hz), 7.29 (d, 2H, J=7.6 Hz), 7.16 (s,1H), 7.06 (d, 1H, J=8 Hz), 6.92 (d, 1H, J=8 Hz), 3.54-3.50 (m, 2H), 3.09(s, 3H), 3.07-2.98 (m, 3H), 2.95-2.82 (m, 3H), 2.68-2.63 (m, 2H),2.46-2.38 (m, 2H), 1.98-1.91 (m, 5H), 1.46-1.36 (m. 3H), 1.29-1.20 (m.7H). LC-MS m/z calcd for C₃₀H₄₀N₄O₃, 504.3; found 505.5 [M+H]⁺. HPLCpurity 99.8%.

Example 82N-hydroxy-4-(3-oxo-3-(4-(((2-phenylcyclopropyl)amino)methyl)piperidin-1-yl)propyl)benzamideTFA Salt

The compound was synthesized using the I-82 following the procedure forExample 2. ¹HNMR (400 MHz, DMSO-d₆): δ 11.09 (s, 1H), 8.90 (bs, 1H),8.72 (bs, 2H), 7.64 (d, 2H, J=8.4 Hz), 7.32-7.25 (m, 4H), 7.22-7.19 (m,1H), 7.19-7.14 (m, 2H), 4.38-4.32 (m, 1H), 3.89-3.83 (m, 1H), 3.00-2.81(m, 4H), 2.83-2.79 (m, 2H), 2.64-2.61 (m, 3H), 2.59-2.40 (m, 2H),1.90-1.80 (m, 1H), 1.73-1.66 (m, 2H), 1.46-1.40 (m, 1H), 1.30-1.25 (m,1H), 1.08-0.95 (m, 1H). LC-MS m/z calcd for C₂₅H₃₁N₃O₃, 421.2; found422.3 [M+H]⁺. HPLC purity 99.5%.

Example 83N-hydroxy-4-(3-oxo-3-(4-((2-phenylcyclopropyl)amino)piperidin-1-yl)propyl)benzamideTFA Salt

The compound was synthesized using the I-83 following the procedure forExample 2. ¹HNMR (400 MHz, DMSO-d₆): δ 11.1 (bs, 1H), 8.95 (bs, 2H),7.64 (d, 2H, J=8.4 Hz), 7.32-7.26 (m, 4H), 7.23-7.20 (m, 1H), 7.19-7.15(m, 2H), 4.46-4.39 (m, 1H), 4.01-3.92 (m, 2H), 3.55-3.40 (m, 1H),3.04-2.90 (m, 2H), 2.88-2.78 (m, 2H), 2.69-2.61 (m, 2H), 2.59-2.52 (m,1H), 2.41-2.31 (m, 1H) 2.08-1.95 (m, 2H), 1.45-1.31 (m, 4H). LC-MS m/zcalcd for C₂₄H₂₉N₃O₃, 407.2; found 408.2 [M+H]⁺. HPLC purity 99.7%.

Example 84N-hydroxy-4-(2-oxo-2-(4-(((2-phenylcyclopropyl)amino)methyl)piperidin-1-yl)ethyl)benzamideTFA Salt

The compound was synthesized using the I-84 following the procedure forExample 2. ¹HNMR (400 MHz, DMSO-d₆): δ 11.13 (bs, 1H), 8.77 (bs, 2H),7.66 (d, 2H, J=8.4 Hz), 7.34-7.23 (m, 4H), 7.22-7.13 (m, 3H), 4.36-4.33(m, 1H), 3.97-3.91 (m, 1H), 3.74 (s, 2H), 3.04-2.92 (m, 4H), 2.61-2.52(m, 1H), 2.41-2.40 (m, 1H), 1.92-1.83 (m, 1H), 1.75-1.63 (m, 2H),1.46-1.40 (m, 1H), 1.30-1.24 (m, 1H), 1.10-0.92 (m, 2H). LC-MS m/z calcdfor C₂₄H₂₉N₃O₃, 407.2; found 408.2 [M+1]⁺. HPLC purity 99.8%.

Example 84 AN-hydroxy-4-(2-oxo-2-(4-((((1R,2S)-2-phenylcyclopropyl)amino)methyl)piperidin-1-yl)ethyl)benzamide TFA Salt

LC-MS m/z calcd for C₂₄H₂₉N₃O₃, 407.2; found 408.2 [M+1]+.

Example 84 BN-hydroxy-4-(2-oxo-2-(4-((((1S,2R)-2-phenylcyclopropyl)amino)methyl)piperidin-1-yl)ethyl)benzamide TFA Salt

LC-MS m/z calcd for C₂₄H₂₉N₃O₃, 407.2; found 408.2 [M+1]⁺.

Example 85N-hydroxy-4-((4-(((2-phenylcyclopropyl)amino)methyl)piperidin-1-yl)sulfonyl)benzamideTFA Salt

The compound was synthesized using the I-85 following the procedure forExample 2. ¹HNMR (400 MHz, DMSO-d₆): δ 11.43 (bs, 1H), 9.21 (bs, 1H),8.71 (bs, 2H), 7.96 (d, 2H, J=8 Hz), 7.80 (d, 2H, J=8 Hz), 7.30-7.24 (m,2H), 7.21-7.16 (m, 1H), 7.14-7.10 (m, 2H), 3.71-3.62 (m, 2H), 3.02-2.87(m, 3H), 2.41-2.32 (m, 1H), 2.31-2.20 (m, 2H), 1.83-1.73 (m, 2H),1.71-1.59 (m, 1H), 1.42-1.36 (m, 1H), 1.31-1.19 (m, 3H). LC-MS m/z calcdfor C₂₂H₂₇N₃O₄S, 429.5; found 430.5 [M+1]⁺. HPLC purity 98.5%.

Example 86N-hydroxy-4-((N-(2-(4-(((2-phenylcyclopropyl)amino)methyl)piperidin-1-yl)ethyl)sulfamoyl)methyl)benzamideTFA Salt

The compound was synthesized using the I-86 following the procedure forExample 48. ¹HNMR (400 MHz, DMSO-d₆): δ 11.22 (bs, 1H), 9.33 (bs, 1H),9.02 (bs, 3H), 7.75 (d, 2H, J=8 Hz), 7.43 (d, 2H, J=8 Hz), 7.32-7.27 (m,2H), 7.24-7.21 (m, 1H), 7.19-7.14 (m, 2H), 4.47 (s, 2H), 3.56-3.49 (m,2H), 3.46-3.25 (m, 2H), 3.21-3.09 (m, 3H), 3.06-2.88 (m, 4H), 2.45-2.40(m, 1H), 2.00-1.85 (m, 3H), 1.51-1.35 (m, 3H), 1.32-1.25 (m, 1H). LC-MSm/z calcd for C₂₅H₃₄N₄O₄S, 486.6; found 487.6 [M+H]⁺. HPLC purity 99.8%.

Example 874-(N-(2-(4-(((2-(4-fluorophenyl)cyclopropyl)amino)methyl)piperidin-1-yl)ethyl)sulfamoyl)-N-hydroxybenzamideTFA Salt

The compound was synthesized using the I-87 following the procedure forExample 48. ¹HNMR (400 MHz, DMSO-d₆): δ 11.42 (bs, 1H), 9.25 (bs, 2H),8.89 (bs, 2H), 8.08 (bs, 1H), 7.89-7.83 (m, 2H), 7.87 (d, 2H, J=8.4 Hz),7.27-7.19 (m, 2H), 7.16-7.08 (m, 2H), 3.56-3.48 (m, 3H), 3.22-3.08 (m,5H), 3.06-2.89 (m, 5H), 1.96-1.81 (m, 3H), 1.48-1.36 (m, 2H), 1.32-1.27(m, 1H). LC-MS m/z calcd for C₂₄H₃₁FN₄O₄S, 490.2; found 491.5 [M+H]⁺.HPLC purity 99.7%.

Example 88N-hydroxy-4-(2-((4-(((2-phenylcyclopropyl)amino)methyl)piperidin-1-yl)sulfonyl)ethyl)benzamideTFA Salt

The compound was synthesized using the I-88 following the procedure forExample 2. ¹HNMR (400 MHz, DMSO-d₆): δ 11.14 (bs, 1H), 8.95 (bs, 1H),8.75 (bs, 2H), 7.66 (d, 2H, J=8 Hz), 7.36 (d, 2H, J=8 Hz), 7.32-7.26 (m,2H), 7.23-7.15 (m, 3H), 3.64-3.58 (m, 2H), 3.37-3.30 (m, 3H), 3.06-2.94(m, 5H), 2.82-2.74 (m, 2H), 2.46-2.38 (m, 2H), 1.82-1.76 (m, 3H),1.48-1.40 (m, 1H), 1.32-1.18 (m, 3H). LC-MS m/z calcd for C₂₄H₃₁N₃O₄S,457.2; found 458.3 [M+H]⁺. HPLC purity 99.1%.

Example 89N-hydroxy-N4-(2-(4-(((2-phenylcyclopropyl)amino)methyl)piperidin-1-yl)ethyl)terephthalamideTFA Salt

The compound was synthesized using the I-89 following the procedure forExample 48. ¹HNMR (400 MHz, DMSO-d₆): δ 11.32 (bs, 1H), 9.06 (bs, 2H),8.86 (bs, 1H), 8.81 (bs, 2H), 7.90 (d, 2H, J=8.4 Hz), 7.84 (d, 2H, J=8Hz), 7.32-7.28 (m, 2H), 7.23-7.21 (m, 1H), 7.18-7.16 (m, 2H), 3.70-3.58(m, 3H), 3.36-3.30 (m, 1H), 3.28-3.20 (m, 2H), 3.08-2.93 (m, 5H),2.02-1.84 (m, 4H), 1.49-1.38 (m, 3H), 1.34-1.28 (m, 1H). LC-MS m/z calcdfor C₂₅H₃₂N₄O₃, 436.3; found 437.5 [M+H]⁺. HPLC purity 99.7%.

Example 90N1-(2-(4-(((2-(3,4-difluorophenyl)cyclopropyl)amino)methyl)piperidin-1-yl)ethyl)-N4-hydroxyterephthalamideTFA Salt

The compound was synthesized using the I-90 following the procedure forExample 48. ¹HNMR (400 MHz, DMSO-d₆): δ 11.32 (bs, 1H), 9.10 (bs, 2H),8.95 (bs, 1H), 8.81 (bs, 2H), 7.90 (d, 2H, J=8.4 Hz), 7.84 (d, 2H, J=8.4Hz), 7.40-7.32 (m, 1H), 7.30-7.25 (m, 1H), 7.29-7.45 (m, 1H), 3.67-3.51(m, 4H), 3.27-3.20 (m, 2H), 3.07-2.94 (m, 5H), 2.00-1.82 (m, 4H),1.48-1.32 (m, 4H). LC-MS m/z calcd for C₂₅H₃₀F₂N₄O₃, 472.2; found 473.5[M+H]⁺. HPLC purity 99.4%.

Example 91N-hydroxy-4-((4-(2-((2-phenylcyclopropyl)amino)acetyl)piperazin-1-yl)methyl)benzamideTFA Salt

The compound was synthesized using the I-91 following the procedure forExample 2. ¹HNMR (400 MHz, DMSO-d₆): δ 11.27 (bs, 1H), 9.29 (bs, 2H),7.82-7.77 (m, 2H), 7.54-7.47 (m, 2H), 7.31-7.24 (m, 2H), 7.22-7.18 (m,1H), 7.14 (d, 2H, J=6.8 Hz), 4.30-4.20 (m, 5H), 3.81-3.72 (m, 4H),3.50-3.32 (m, 1H), 2.90-2.81 (m, 2H), 2.01-1.92 (m, 1H), 1.47-1.28 (m,1H), 1.74-1.51 (m, 1H), 1.27-1.21 (m, 1H). LC-MS m/z calcd forC₂₃H₂₈N₄O₃, 408.2; found 409.3 [M+H]⁺. HPLC purity 98.7%.

Example 92N-hydroxy-4-(3-oxo-3-(4-(2-((2-phenylcyclopropyl)amino)acetyl)piperazin-1-yl)propyl)benzamideTFA Salt

The compound was synthesized using the I-92 following the procedure forExample 2. ¹HNMR (400 MHz, DMSO-d₆): δ 11.10 (s, 1H), 9.21 (bs, 2H),8.96 (bs, 1H), 7.64 (d, 2H, J=8.4 Hz), 7.35-7.26 (m, 4H), 7.23-7.18 (m,1H), 7.18-7.14 (m, 2H), 4.28-4.20 (m, 2H), 3.54-3.35 (m, 8H), 2.88-2.81(m, 3H), 2.70-2.62 (m, 2H), 1.50-1.44 (m, 1H), 1.30-1.21 (m, 2H). LC-MSm/z calcd for C₂₅H₃₀N₄O₄, 450.1; found 451.2 [M+H]⁺. HPLC purity 92.7%.

Example 93N-hydroxy-4-(3-(1-(2-((2-phenylcyclopropyl)amino)acetyl)piperidin-4-yl)propyl)benzamideTFA Salt

The compound was synthesized using the I-93 following the procedure forExample 2. ¹HNMR (400 MHz, DMSO-d₆): δ 11.09 (s, 1H), 9.11 (bs, 2H),8.91 (bs, 1H), 7.65 (d, 2H, J=8.2 Hz), 7.29-7.13 (m, 7H), 4.33-4.13 (m,3H), 3.65-3.62 (m, 1H), 3.31-2.84 (m, 2H), 2.87-2.82 (m, 1H), 2.65-2.57(m, 3H), 1.73-1.65 (m, 2H), 1.58-1.44 (m, 4H), 1.26-1.16 (m, 3H),1.06-0.98 (m, 1H), 0.90-0.82 (m, 1H). LC-MS m/z calcd for C₂₆H₃₃N₃O₃,435.2; found 436.2 [M+H]⁺. HPLC purity 99.9%.

Example 94N-hydroxy-4-(3-(2-oxo-4-(((2-phenylcyclopropyl)amino)methyl)piperidin-1-yl)propyl)benzamide TFA Salt

The compound was synthesized using the I-94 following the procedure forExample 2. LC-MS m/z calcd for C₂₅H₃₁N₃O₃, 421.5; found 422.5 [M+H]⁺.

Example 95 N-hydroxy-4-(2-((2-phenylcyclopropyl)amino)ethoxy)benzamideTFA Salt

The compound was synthesized using the I-95 following the procedure forExample 2. ¹HNMR (400 MHz, DMSO-d₆): δ 11.06 (bs, 1H), 9.20 (bs, 2H),7.73 (d, 2H, J=8.8 Hz), 7.29-7.22 (m, 2H), 7.26-7.18 (m, 1H), 7.12 (d,2H, J=9.2 Hz), 6.99 (d, 2H, J=8.8 Hz), 4.35-4.25 (m, 2H), 3.55-3.48 (m,2H), 3.08-3.01 (m, 1H), 2.46-2.39 (m, 1H), 1.49-1.43 (m, 1H), 1.34-1.26(m, 1H). LC-MS m/z calcd for C₁₈H₂₀N₂O₃, 312.1; found 313.1 [M+H]⁺. HPLCpurity 99.6%.

Example 966-(2-(4-(((2-(4-fluorophenyl)cyclopropyl)amino)methyl)piperidin-1-yl)ethoxy)-N-hydroxynicotinamideTFA Salt

The compound was synthesized using the I-96 following the procedure forExample 2. ¹HNMR (400 MHz, DMSO-d₆): δ 11.01 (bs, 1H), 9.17 (bs, 1H),8.94 (bs, 2H), 8.29 (s, 1H), 7.77 (dd, J=9.2, 2.8 Hz, 1H), 7.28-7.18 (m,2H), 7.13 (t, J=8.8 Hz, 2H), 6.46 (d, J=9.6 Hz, 1H), 4.25-4.35 (m, 2H),3.72-3.59 (m, 2H), 3.45-3.30 (m, 2H), 3.28-3.14 (m, 1H), 3.08-2.90 (m,5H), 2.04-1.85 (m, 3H), 1.48-1.24 (m, 4H). LC-MS m/z calcd forC₂₃H₂₉FN₄O₃, 428.2; found 429.2 [M+H]⁺. HPLC purity 99.6%.

Example 97N-hydroxy-6-(2-(4-(((2-phenylcyclopropyl)amino)methyl)piperidin-1-yl)ethoxy)nicotinamideTFA Salt

The compound was synthesized using the I-97 following the procedure forExample 2. ¹HNMR (400 MHz, DMSO-d₆): δ 11.02 (bs, 1H), 9.26 (bs, 1H),9.03 (bs, 2H), 8.30 (d, J=1.6 Hz, 1H), 7.77 (dd, J=9.6, 2.4 Hz, 1H),7.30 (t, J=7.2 Hz, 2H), 7.24-7.16 (m, 3H), 6.46 (d, J=10 Hz, 1H),4.35-4.28 (m, 2H), 3.80-3.62 (m, 3H), 3.43-3.37 (m, 3H), 3.24-3.12 (m,1H), 3.08-2.91 (m, 4H), 2.04-1.88 (m, 2H), 1.52-1.35 (m, 3H), 1.33-1.25(m, 1H). LC-MS m/z calcd for C₂₃H₃₀N₄O₃, 410.2; found 411.2 [M+H]⁺. HPLCpurity=98.2%.

Example 986-(2-(4-(((2-(4′-fluoro-[1,1′-biphenyl]-4-yl)cyclopropyl)amino)methyl)piperidin-1-yl)ethoxy)-N-hydroxynicotinamideTFA Salt

The compound was synthesized using the I-98 following the procedure forExample 2. ¹HNMR (400 MHz, DMSO-d₆): δ 11.02 (bs, 1H), 9.14 (bs, 1H),8.93 (bs, 3H), 8.30 (s, 1H), 7.82-7.75 (m, 1H), 7.70-7.64 (m, 2H), 7.58(d, J=8.4 Hz, 2H), 7.32-7.24 (m, 4H), 6.46 (d, J=9.2 Hz, 1H), 4.34-4.28(m, 2H), 3.71-3.65 (m, 3H), 3.26-3.24 (m, 1H), 3.08-2.96 (m, 3H),2.57-2.54 (m, 3H), 2.02-1.93 (m, 3H), 1.52-1.39 (m, 4H). LC-MS m/z calcdfor C₂₉H₃₃FN₄O₃, 504.2; found 505.2[M+H]⁺. HPLC purity 98.2%.

Example 99N-hydroxy-4-(2-(4-(((2-phenylcyclopropyl)amino)methyl)piperidin-1-yl)ethoxy)benzamideTFA Salt

The compound was synthesized using the I-99 following the procedure forExample 2. ¹HNMR (400 MHz, DMSO-d₆): δ 11.0 (bs, 1H), 9.5 (bs, 1H), 8.9(bs, 2H), 7.75 (d, 2H, J=8 Hz), 7.32-7.26 (m, 2H), 7.23-7.15 (m, 3H),7.03 (d, 2H, J=8 Hz), 4.41-4.35 (m, 2H), 3.52-3.45 (m, 2H), 3.35-3.28(m, 2H), 3.10-2.95 (m, 5H), 2.00-1.91 (m, 3H), 1.51-1.41 (m, 3H),1.32-1.25 (m, 1H). LC-MS m/z calcd for C₂₄H₃₁N₃O₃, 409.2; found 410.2[M+H]⁺. HPLC purity 99.1%.

Example 100N-hydroxy-4-(3-(4-(((2-phenylcyclopropyl)amino)methyl)piperidin-1-yl)propoxy)benzamideTFA Salt

The compound was synthesized using the I-100 following the procedure forExample 2.

¹HNMR (400 MHz, DMSO-d₆): δ 11.04 (s, 1H), 9.12 (bs, 1H), 8.87 (bs, 1H),7.72 (d, 2H, J=8.4 Hz), 7.34-7.26 (m, 2H), 7.24-7.20 (m, 1H), 7.21-7.15(m, 2H), 6.96 (d, 2H, J=8.8 Hz), 4.11-4.08 (m, 2H), 3.60-3.51 (m, 2H),3.23-3.18 (m, 2H), 3.05-3.01 (m, 2H), 2.98-2.92 (m, 2H), 2.45-2.40 (m,3H), 2.14-2.09 (m. 2H), 1.98-1.93 (m, 3H), 1.48-1.32 (m, 3H), 1.32-1.28(m, 1H). LC-MS m/z calcd for C₂₅H₃₃N₃O₃, 423.2; found 424.2 [M+H]⁺. HPLCpurity 99.2%.

Example 101 N-hydroxy-4-(3-((2-phenylcyclopropyl)amino)propoxy)benzamideTFA Salt

The compound was synthesized using the I-101 following the procedure forExample 2.

¹HNMR (400 MHz, DMSO-d₆): δ 11.03 (s, 1H), 8.92 (bs, 3H), 7.72 (d, 2H,J=8.9 Hz), 7.31-7.26 (m, 2H), 7.35-7.20 (m, 1H), 7.18-7.14 (m, 2H), 6.96(m, 2H), 4.13-4.07 (m, 2H), 3.28-3.21 (bs, 2H), 3.06-2.98 (m, 1H),2.43-2.38 (m, 1H), 2.11-2.03 (m, 2H), 1.49-1.41 (m, 1H), 1.33-1.26 (m,1H). LC-MS m/z calcd for C₁₉H₂₂N₂O₃, 326.3; found 327.3 [M+H]⁺. HPLCpurity 99.7%.

Example 1022-((2-(4-(((2-(4-fluorophenyl)cyclopropyl)amino)methyl)piperidin-1-yl)ethyl)amino)-N-hydroxypyrimidine-5-carboxamideTFA Salt

The compound was synthesized using the I-102 following the procedure forExample 2.

¹HNMR (400 MHz, DMSO-d₆): δ11.07 (bs, 1H), 9.36 (bs, 1H), 9.14 (bs, 2H),8.66 (s, 2H), 7.87 (bs, 1H), 7.26-7.19 (m, 2H), 7.15-7.08 (m, 2H),3.72-3.58 (m, 4H), 3.38-3.12 (m, 3H), 3.08-2.88 (m, 5H), 2.00-1.82 (m,3H) 1.52-1.38 (m, 3H), 1.33-1.20 (m, 1H). LC-MS m/z calcd forC₂₂H₂₉N₆O₂, 428.2; found 429.3 [M+H]⁺. HPLC purity 99.8%.

Example 1035-(2-((2-(4-fluorophenyl)cyclopropyl)amino)acetyl)-N-hydroxy-4,5,6,7-tetrahydrothieno[3,2-c]pyridine-2-carboxamide TFA Salt

The compound was synthesized using the I-103 following the procedure forExample 2.

¹HNMR (400 MHz, DMSO-d₆): δ 11.16 (bs, 1H), 9.22 (bs, 2H), 9.06 (bs,1H), 7.41-7.35 (m, 1H), 7.25-7.16 (m, 2H), 7.13-7.07 (m, 2H) 4.59-4.48(m, 2H), 4.43-4.29 (m, 2H), 3.85-3.78 (m, 1H), 3.70-3.65 (m, 1H),2.96-2.90 (m, 1H), 2.88-2.78 (m, 2H), 1.51-1.48 (m, 1H), 1.31-1.20 (m,1H); LC-MS m/z calcd for C₁₉H₂₀FN₃O₃S, 389.1; found 390.1 [M+H]⁺. HPLCpurity 99.3%.

Example 103A5-(2-(((1R,2S)-2-(4-fluorophenyl)cyclopropyl)amino)acetyl)-N-hydroxy-4,5,6,7-tetrahydrothieno[3,2-c]pyridine-2-carboxamideTFA Salt

LC-MS m/z calcd for C₁₉H₂₀FN₃O₃S, 389.1; found 390.1 [M+H]⁺

Example 103B5-(2-(((1S,2R)-2-(4-fluorophenyl)cyclopropyl)amino)acetyl)-N-hydroxy-4,5,6,7-tetrahydrothieno[3,2-c]pyridine-2-carboxamideTFA Salt

LC-MS m/z calcd for C₁₉H₂₀FN₃O₃S, 389.1; found 390.1 [M+H]⁺

Example 1042-(2-((2-(4-fluorophenyl)cyclopropyl)amino)acetyl)-N-hydroxy-1,2,3,4-tetrahydroisoquinoline-7-carboxamideTFA Salt

The compound was synthesized using the I-104 following the procedure forExample 2.

¹HNMR (400 MHz, DMSO-d₆): δ 11.16 (bs, 1H), 9.22 (bs, 2H), 8.96 (bs,1H), 7.62-7.51 (m, 2H), 7.28-7.15 (m, 3H), 7.13-7.08 (m, 2H), 4.66-4.64(m, 2H), 4.35-4.31 (m, 2H), 3.75-3.70 (m, 1H), 3.64-3.61 (m, 2H),2.96-2.91 (m, 1H), 2.89-2.80 (m, 2H), 1.49-1.46 (m, 1H), 1.29-1.25 (m,1H). LC-MS m/z calcd for C₂₁H₂₂FN₃O₃, 383.2; found 384.1 [M+H]⁺. HPLCpurity 99.5%.

Example 104A2-(2-(((1S,2R)-2-(4-fluorophenyl)cyclopropyl)amino)acetyl)-N-hydroxy-1,2,3,4-tetrahydroisoquinoline-7-carboxamideTFA Salt

LC-MS m/z calcd for C₂₁H₂₂FN₃O₃, 383.2; found 384.1 [M+H]⁺.

Example 104B2-(2-(((1R,2S)-2-(4-fluorophenyl)cyclopropyl)amino)acetyl)-N-hydroxy-1,2,3,4-tetrahydroisoquinoline-7-carboxamideTFA Salt

LC-MS m/z calcd for C₂₁H₂₂FN₃O₃, 383.2; found 384.1 [M+H]⁺.

Example 1055-(4-((2-(4-fluorophenyl)cyclopropyl)amino)butanoyl)-N-hydroxy-4,5,6,7-tetrahydrothieno[3,2-c]pyridine-2-carboxamideTFA Salt

The compound was synthesized using the I-105 following the procedure forExample 2.

¹HNMR (400 MHz, DMSO-d₆): δ 11.08 (bs, 1H), 9.04 (bs, 1H), 8.84 (bs,2H), 7.35 (s, 1H), 7.28-7.16 (m, 2H), 7.11 (t, J=8.4 Hz, 2H), 4.50 (s,2H), 3.80-3.66 (m, 2H), 3.15-3.05 (m, 2H), 3.00-2.90 (m, 1H), 2.92-2.80(m, 1H), 2.82-2.70 (m, 1H), 2.60-2.51 (m, 2H), 2.42-2.34 (m, 1H),1.92-1.75 (m, 2H), 1.40 (q, 1H), 1.25 (q, 1H). LC-MS m/z calcd forC₂₁H₂₄FN₃O₃S, 417.2; found 418.4 [M+H]⁺; HPLC purity 99.5%.

Example 1065-(4-(4-(((2-(4-fluorophenyl)cyclopropyl)amino)methyl)piperidin-1-yl)butanoyl)-N-hydroxy-4,5,6,7-tetrahydrothieno[3,2-c]pyridine-2-carboxamideTFA Salt

The compound was synthesized using the I-106 following the procedure forExample 48. ¹HNMR (400 MHz, DMSO-d₆): δ 11.04 (bs, 1H), 9.05 (bs, 2H),8.84 (bs, 2H), 7.34 (s, 1H), 7.22-7.20 (m, 2H), 7.15-7.11 (m, 2H), 4.51(s, 2H), 3.77-3.70 (m, 2H), 3.55-3.50 (m, 2H), 3.06-3.00 (m, 4H),2.97-2.86 (m, 4H), 2.77-2.75 (m, 1H), 2.58-2.56 (m, 2H), 2.00-1.86 (m,6H), 1.48-1.28 (m, 4H). LC-MS m/z calcd for C₂₇H₃₅FN₄O₃S, 514.2; found515.3 [M+H]⁺. HPLC purity 99.2%.

Example 1072-(4-((2-(4-fluorophenyl)cyclopropyl)amino)butanoyl)-N-hydroxy-1,2,3,4-tetrahydroisoquinoline-7-carboxamideTFA Salt

The compound was synthesized using the I-107 following the procedure forExample 2.

¹HNMR (400 MHz, DMSO-d₆): δ 11.13 (bs, 1H), 8.86 (bs, 2H), 8.92 (bs,2H), 7.59-7.48 (m, 2H), 7.24-7.19 (m, 3H), 7.14-7.06 (t, J=8.4 Hz, 2H),4.63 (d, J=10 Hz, 2H), 3.69-3.53 (m, 2H), 3.14-3.05 (m, 2H), 2.98-2.95(m, 2H), 2.82-2.76 (m, 1H), 2.58-2.56 (m, 2H), 2.45-2.38 (m, 1H),1.90-1.82 (m, 2H), 1.45-1.38 (m, 1H), 1.32-1.24 (m, 1H). LC-MS m/z calcdfor C₂₃H₂₆FN₃O₃, 411.2; found 412.2[M+H]⁺. HPLC purity 99.7%.

Example 1082-(4-((2-(4-fluorophenyl)cyclopropyl)amino)butanoyl)-N-hydroxyisoindoline-5-carboxamideTFA Salt

The compound was synthesized using the I-108 following the procedure forExample 2.

¹HNMR (400 MHz, DMSO-d₆): δ 11.19 (bs, 1H), 8.79 (bs, 2H), 7.75-7.62 (m,2H), 7.43-7.35 (m, 1H), 7.25-7.21 (m, 2H), 7.15-7.10 (m, 2H), 4.81 (s,2H), 4.66 (s, 2H), 3.16-3.10 (m, 2H), 3.02-2.96 (m, 1H), 2.43-2.36 (m,3H), 1.94-1.88 (m, 2H), 1.44-1.40 (m, 1H), 1.33-1.27 (m, 1H). LC-MS m/zcalcd for C₂₂H₂₄FN₃O₃, 397.2; found 398.2 [M+H]⁺. HPLC purity 99.2%.

Example 109N-hydroxy-2-(4-(4-(((2-phenylcyclopropyl)amino)methyl)piperidin-1-yl)butanoyl)isoindoline-5-carboxamideTFA Salt

The compound was synthesized using the I-109 following the procedure forExample 48. ¹HNMR (400 MHz, DMSO-d₆): δ 11.20 (bs, 1H), 9.14 (bs, 2H),8.88 (bs, 3H), 7.68 (d, 1H, J=8 Hz), 7.43-7.38 (m, 1H), 7.32-7.28 (m,2H), 7.24-7.16 (m, 3H), 4.84 (s, 2H), 4.66 (s, 2H), 3.60-3.54 (m, 2H),3.34-3.15 (m, 1H), 3.10-2.88 (m, 8H), 2.01-1.71 (m, 6H), 1.50-1.27 (m,4H). LC-MS m/z calcd for C₂₈H₃₆N₄O₃, 476.3; found 477.6 [M+H]⁺. HPLCpurity 99.6%.

Example 110N-hydroxy-2-(3-(4-(((2-phenylcyclopropyl)amino)methyl)piperidin-1-yl)propyl)thiazole-4-carboxamideTFA Salt

The compound was synthesized using the I-110 following the procedure forExample 48. ¹HNMR (400 MHz, DMSO-d₆): δ 11.32 (bs, 1H), 9.46 (bs, 1H),9.09 (bs, 2H), 8.10 (s, 1H), 7.32-7.26 (m, 2H), 7.23-7.13 (m, 3H),3.56-3.51 (m, 2H), 3.30-2.83 (m, 9H), 2.43-2.40 (m, 1H), 2.17-2.08 (m,2H), 2.06-1.71 (m, 3H), 1.50-1.35 (m, 3H), 1.30-1.25 (m, 1H). LC-MS m/zcalcd for C₂₂H₃₀N₄O₂S, 414.2; found 415.5 [M+H]⁺. HPLC purity 99.5%.

Example 1112-(3-(4-(((2-(4′-fluoro-[1,1′-biphenyl]-4-yl)cyclopropyl)amino)methyl)piperidin-1-yl)propyl)-N-hydroxythiazole-4-carboxamideTFA Salt

The compound was synthesized using the I-111 following the procedure forExample 48. ¹HNMR (400 MHz, DMSO-d₆): δ 10.98 (bs, 1H), 9.13 (bs, 2H),8.24 (bs, 2H), 8.13 (s, 1H), 7.69-7.64 (m, 2H), 7.58 (d, 2H, J=8.6 Hz),7.30-7.25 (m, 4H), 3.60-3.55 (m, 2H), 3.19-3.12 (m, 3H), 3.10-3.06 (m,6H), 2.98-2.86 (m, 3H), 2.18-2.09 (m, 2H), 2.00-1.94 (m, 2H), 1.50-1.44(m, 1H), 1.42-1.36 (m, 2H). LC-MS m/z calcd for C₂₈H₃₃FN₄O₂S, 508.2;found 509.6 [M+H]⁺. HPLC purity 99.6%.

Example 112N-hydroxy-2-(3-(4-(((2-phenylcyclopropyl)amino)methyl)piperidin-1-yl)propyl)thiazole-5-carboxamideTFA Salt

The compound was synthesized using the I-112 following the procedure forExample 48. ¹HNMR (400 MHz, DMSO-d₆): δ 11.32 (bs, 1H), 9.45 (bs, 1H),9.09 (bs, 2H), 8.10 (s, 1H), 7.31-7.25 (m, 2H), 7.21-7.15 (m, 3H),3.56-3.50 (m, 2H), 3.31-3.10 (m, 3H), 3.09-3.02 (m, 3H), 2.97-2.86 (m,2H), 2.47-2.42 (m, 2H), 2.15-2.07 (m, 2H), 2.00-1.89 (m, 2H), 1.80-1.70(m, 1H), 1.50-1.35 (m, 3H), 1.32-1.27 (m, 1H). LC-MS m/z calcd forC₂₂H₃₀N₄O₂S, 415.2; found 416.5 [M+H]⁺. HPLC purity 99.3%.

Example 113N-hydroxy-2-(3-(4-(((2-phenylcyclopropyl)amino)methyl)piperidin-1-yl)propyl)oxazole-4-carboxamideTFA Salt

The compound was synthesized using the I-113 following the procedure forExample 48. ¹HNMR (400 MHz, DMSO-d₆): δ 10.92 (bs, 1H), 9.49 (bs, 1H),9.09 (bs, 2H), 8.47 (s, 1H), 7.32-7.14 (m, 5H), 3.60-3.51 (m, 2H),3.32-3.12 (m, 3H), 3.08-2.81 (m, 6H), 2.15-1.73 (m, 6H), 1.50-1.37 (m,3H), 1.30-1.23 (m, 1H). LC-MS m/z calcd for C₂₂H₃₀N₄O₃, 398.2; found399.5 [M+H]⁺. HPLC purity 99.6%.

Example 114(E)-N-hydroxy-4-(3-oxo-3-(4-(((2-phenylcyclopropyl)amino)methyl)piperidin-1-yl)prop-1-en-1-yl)benzamideTFA Salt

The compound was synthesized using the I-114 following the procedure forExample 2.

¹HNMR (400 MHz, DMSO-d₆): δ 11.24 (bs, 1H), 9.02 (bs, 1H), 8.76 (bs,2H), 7.79-7.72 (m, 4H), 7.47 (d, 1H, J=15 Hz), 7.33 (d, 1H, J=15 Hz),7.33-7.27 (m, 2H), 7.22-7.15 (m, 3H), 4.47-4.42 (m, 1H), 4.33-4.27 (m,1H), 3.11-2.97 (m, 4H), 2.72-2.64 (m, 1H), 2.48-2.38 (m, 1H), 2.00-1.91(m, 1H), 1.84-1.75 (m, 2H), 1.48-1.41 (m, 1H), 1.33-1.27 (m, 1H),1.19-1.09 (m, 2H). LC-MS m/z calcd for C₂₅H₂₉N₃O₃, 419.2; found 420.2[M+1]⁺. HPLC purity 99.8%.

Example 114AN-hydroxy-4-((E)-3-oxo-3-(4-((((1R,2S)-2-phenylcyclopropyl)amino)methyl)piperidin-1-yl)prop-1-en-1-yl)benzamideTFA Salt

LC-MS m/z calcd for C₂₅H₂₉N₃O₃, 419.2; found 420.2 [M+1]⁺.

Example 114BN-hydroxy-4-((E)-3-oxo-3-(4-((((1S,2R)-2-phenylcyclopropyl)amino)methyl)piperidin-1-yl)prop-1-en-1-yl)benzamideTFA Salt

LC-MS m/z calcd for C₂₅H₂₉N₃O₃, 419.2; found 420.2 [M+1]⁺.

Example 1154-((E)-3-(4-((((1S,2R)-2-(4-fluorophenyl)cyclopropyl)amino)methyl)piperidin-1-yl)-3-oxoprop-1-en-1-yl)-N-hydroxybenzamideTFA Salt

The compound was synthesized using the I-115 following the procedure forExample 2.

LC-MS m/z calcd for C₂₅H₂₈FN₃O₃, 437.5; found 438.5 [M+1]⁺.

Example 115A4-((E)-3-(4-((((1R,2S)-2-(4-fluorophenyl)cyclopropyl)amino)methyl)piperidin-1-yl)-3-oxoprop-1-en-1-yl)-N-hydroxybenzamideTFA Salt

LC-MS m/z calcd for C₂₅H₂₈FN₃O₃, 437.5; found 438.5 [M+1]⁺.

Example 116(E)-4-(3-(4-(((2-(4-(3,5-dimethylisoxazol-4-yl)phenyl)cyclopropyl)amino)methyl)piperidin-1-yl)-3-oxoprop-1-en-1-yl)-N-hydroxybenzamideTFA Salt

The compound was synthesized using the I-116 following the procedure forExample 2.

¹HNMR (400 MHz, DMSO-d₆): δ 11.24 (s, 1H), 9.02 (s, 1H), 8.84-8.72 (bs,2H), 7.76 (m, 4H), 7.48 (d, J=16.0 Hz, 1H), 7.34 (d, J=16.0 Hz, 1H),7.30-7.26 (m, 4H), 4.4-4.3 (dd, 2H), 3.15-2.98 (m, 4H), 2.75-2.65 (m,1H), 2.45-2.40 (m, 1H), 2.35 (s, 3H), 2.18 (s, 3H), 2.04-1.9 (m, 1H),1.88-1.75 (m, 1H), 1.52-1.44 (m, 1H), 1.40-1.30 (q, J=6.8 Hz, 1H),1.25-1.08 (m, 2H). LC-MS m/z calcd for C₃₀H₃₄N₄O₄, 514.2; found 515.2[M+H]⁺. HPLC purity 99.8%.

Example 117(E)-N-hydroxy-4-(3-oxo-3-(4-(((2-(4-(pyrimidin-5-yl)phenyl)cyclopropyl)amino)methyl)piperidin-1-yl)prop-1-en-1-yl)benzamideTFA Salt

The compound was synthesized using the I-117 following the procedure forExample 2.

¹HNMR (400 MHz, DMSO-d₆): δ 11.24 (bs, 1H), 9.16 (s, 1H), 9.11 (s, 2H),8.92-8.72 (bs, 2H), 7.83-7.73 (m, 4H), 7.69 (d, 2H, J=8.4 Hz), 7.52-7.43(m, 1H), 7.40-7.33 (m, J=8.4 Hz, 2H), 7.30 (d, J=16 Hz, 1H), 4.55-4.26(m, 2H), 3.18-3.00 (m, 4H), 2.75-2.60 (m, 2H), 2.05-1.90 (m, 1H),1.88-1.72 (m, 2H), 1.58-1.48 (m, 1H), 1.42-1.34 (m, 1H), 1.25-1.08 (m,2H). LC-MS m/z calcd for C₂₉H₃₁N₅O₃, 497.2; found 498.2 [M+H]⁺. HPLCpurity 99.6%.

Example 118(E)-4-(3-(3-(((2-(4-fluorophenyl)cyclopropyl)amino)methyl)azetidin-1-yl)-3-oxoprop-1-en-1-yl)-N-hydroxybenzamideTFA Salt

The compound was synthesized using the I-118 following the procedure forExample 2.

¹HNMR (400 MHz, DMSO-d₆): δ 11.25 (bs, 1H), 9.03 (bs, 1H), 8.91 (bs,2H), 7.81-7.61 (m, 4H), 7.45 (d, J=16 Hz, 1H), 7.26-7.21 (m, 2H),7.16-7.11 (m, 2H), 6.74 (d, J=15 Hz, 1H), 4.47-4.40 (m, 1H), 4.10-4.02(m, 2H), 3.81-3.76 (m, 1H), 3.48-3.43 (m, 3H), 3.10-2.93 (m, 2H),1.44-1.40 (m, 1H), 1.33-1.25 (m, 1H). LC-MS m/z calcd for C₂₃H₂₄FN₃O₃,409.2; found 410.1 [M+H]⁺. HPLC purity 98.5%.

Example 119(E)-N-hydroxy-4-(3-(3-(((2-(4-(1-methyl-1H-pyrazol-4-yl)phenyl)cyclopropyl)amino)methyl)azetidin-1-yl)-3-oxoprop-1-en-1-yl)benzamideTFA Salt

The compound was synthesized using the I-119 following the procedure forExample 2.

¹HNMR (400 MHz, DMSO-d₆): δ 11.24 (bs, 1H), 9.01 (bs, 1H), 8.91 (bs,2H), 8.08 (s, 1H), 7.81 (s, 1H), 7.56-7.70 (m, 4H), 7.50-7.43 (m, 3H),7.15 (d, 2H, J=8 Hz), 6.74 (d, 1H, J=14 Hz), 4.46-4.38 (m, 1H),4.08-4.02 (m, 2H), 3.83 (m, 3H), 3.80-3.77 (m, 1H), 3.01-2.94 (m, 2H),2.47-2.35 (m, 3H), 1.46-1.40 (m, 1H), 1.35-1.28 (m, 1H). LC-MS m/z calcdfor C₂₇H₂₉N₅O₃, 471.23; found 472.2 [M+H]⁺. HPLC purity 99.8%.

Example 120(E)-N-(2-aminophenyl)-3-(4-(((2-4-fluorophenyl)cyclopropyl)amino)methyl)phenyl)acrylamideTFA Salt

Step 1:(E)-3-(4-(((tert-butoxycarbonyl)(2-(4-fluorophenyl)cyclopropyl)amino)methyl)phenyl)acrylicAcid (XC)

To a stirred solution of (E)-methyl3-(4-(((tetra-butoxycarbonyl)(2-(4-florophenyl)cyclopropl)amino)methyl)phenyl)acrylate(I-2, 0.38 g, 0.89 mmol) in methanol and water mixture (20 mL, 4:1) wasadded sodium hydroxide (0.11 g, 2.68 mmol) at room temperature and theresulting mixture was stirred at that temperature for 1 h. The progressof the reaction was monitored by TLC. After completion of reaction,solvent was evaporated and washed with ethylacetate. The reactionmixture was acidified with 2N HCl and extracted with dichloromethane andthe organic portion was washed with water and brine, dried over sodiumsulphate and concentrated under reduced pressure to get the crude toafford the titled product as off white solid (XC, 0.31 g, 86.2%), LC-MSm/z calcd for C₂₄H₂₆FNO₄, 411.2; found 311.2 [M-Boc]⁺.

Step 2: (E)-tert-butyl4-(3-((2-aminophenyl)amino)-3-oxoprop-1-en-1-yl)benzyl(2-(4-fluorophenyl)cyclopropyl)carbamate(XCI)

To a stirred solution of(E)-3-(4-(((tert-Butoxycarbonyl)-(2-(4-fluorophenyl)cyclopropyl)amino)methyl)phenyl)acrylicacid (XC, 0.28 g, 0.68 mmol) in dry dichloromethane (8 mL), was addedbenzene-1,2-diamine (0.22 g, 2.04 mmol), thentriethylamine (0.28 mL,2.04 mmol), cooled to 0° C. and T3P (0.50 mL, 1.70 mmol) was added andthe resulting mixture was stirred at room temperature for 3 h. Aftercompletion of the reaction, the mixture was quenched with ice-water andextracted with dichloromethane. The organic layer was washed with water,brine, dried over sodium sulphate and concentrated under reducedpressure to afford the crude compound which was purified by flash columnchromatography using ethylacetate-hexane gradient to afford the titledproduct as yellow semi solid. (XCI, 0.26 g, 68%). LC-MS m/z calcd forC₃₀H₃₂FN₃O₃, 501.2; found 502.3 [M+H]⁺.

Step 3: (E)-N-(2-aminophenyl)-3-(4-(((2-(4fluorophenyl)cyclopropyl)amino)methyl)phenyl)acrylamide—Example 120

To a stirred solution of (E)-tetra-butyl4(3-((2-aminophenyl)amino)-3-oxoprop-1-en-1-yl)benzyl(2-(4-flurophenyl)cyclopropyl)carbamate(XCI, 0.26 g, 0.52 mmol) in dry dichloromethane (10 mL) was addedtrifluoro acetic acid (0.63 mL, 8.30 mmol) at 0° C. and the resultingmixture was stirred at room temperature for 1 h. The progress of thereaction was monitored by TLC. The solvent was concentrated underreduced pressure to get the crude product which was purified byreverse-phase HPLC using Chemsil C₁₈ (250 mm×4.6 mm×5mic) column with0.1% TFA in water:ACN to afford the pure product as pale-yellow solid(Example 120: 0.204 g, 96%). ¹HNMR (400 MHz, DMSO-d₆): δ 9.43 (bs, 1H),9.34 (bs, 2H), 7.65-7.62 (m, 2H), 7.57-7.49 (m, 3H), 7.34-7.30 (m, 1H),7.19-7.06 (m, 4H), 6.95-6.89 (m, 2H), 6.78-6.74 (m, 1H), 6.62-6.56 (m,1H), 4.36-4.32 (m, 2H), 2.93-2.89 (m, 1H), 2.46-2.35 (m, 1H), 1.49-1.39(m, 1H), 1.35-1.25 (m, 1H). LC-MS calcd for C₂₅H₂₄FN₃O, 401.2; found402.4 [M+H]⁺. HPLC purity 94.8%.

Example 121N-(2-aminophenyl)-4-(3-(4-(((2-phenylcyclopropyl)amino)methyl)piperidin-1-yl)propyl)benzamideTFA Salt

The compound was synthesized using I-121 following the procedure forexample 120. ¹HNMR (400 MHz, DMSO-d₆): δ 9.79 (bs, 1H), 9.59 (bs, 1H),9.13 (bs, 2H), 7.94 (d, 2H, J=7.6 Hz), 7.36 (d, 2H, J=7.6 Hz), 7.31-7.27(m, 2H), 7.25-7.13 (m, 4H), 7.09-7.01 (m, 1H), 6.93-6.89 (m, 1H),6.79-6.73 (m, 1H), 3.59-3.48 (m, 2H), 3.08-2.82 (m, 7H), 2.74-2.67 (m,2H), 2.06-1.87 (m, 6H), 1.50-1.38 (m, 3H), 1.30-1.20 (m, 1H). LC-MS m/zcalcd for C₃₁H₃₈N₄O, 482.3; found 483.3 [M+H]⁺. HPLC purity 92.6%.

Example 122N-(2-aminophenyl)-4-(3-(4-(((2-(4-fluorophenyl)cyclopropyl)amino)methyl)piperidin-1-yl)propyl)benzamideTFA Salt

The compound was synthesized using I-122 following the procedure forexample 120. ¹HNMR (400 MHz, DMSO-d₆): δ 9.73 (bs, 1H), 9.60 (bs, 1H),9.14 (bs, 2H), 7.94 (d, 2H, J=7.6 Hz), 7.36 (d, 2H, J=7.6 Hz), 7.24-7.17(m, 3H), 7.16-7.08 (m, 2H), 7.05-7.00 (m, 1H), 6.90-6.85 (m, 1H),6.75-6.68 (m, 1H), 3.56-3.48 (m, 2H), 3.30-3.21 (m, 1H), 3.08-2.98 (m,4H), 2.95-2.82 (m, 3H), 2.72-2.65 (m, 2H), 2.06-1.87 (m, 5H), 1.50-1.38(m, 3H), 1.30-1.20 (m, 1H). LC-MS m/z calcd for C₃₁H₃₇FN₄O, 500.6; found501.2 [M+H]⁺. HPLC purity 92.6%.

Example 123N-(2-aminophenyl)-4-(3-(4-(((2-(4methoxyphenyl)cyclopropyl)amino)methyl)piperidin-1-yl)propyl)benzamideTFA Salt

The compound was synthesized using I-123 following the procedure forexample 120. ¹HNMR (400 MHz, DMSO-d₆): δ 9.64 (s, 1H), 9.30 (bs, 1H),8.92 (bs, 1H), 7.93 (d, 2H J=8 Hz), 7.36 (d, 2H, J=8 Hz), 7.15 (d, 2H,J=7.6 Hz), 7.08 (d, 2H, J=8 Hz), 6.99-6.96 (m, 1H), 6.86-6.81 (m, 2H),6.65-6.60 (m, 1H), 3.70 (s, 3H), 3.54-3.50 (m, 3H), 3.08-3.00 (m, 4H),2.94-2.82 (m, 3H), 2.75-2.68 (m, 2H), 2.42-2.34 (m, 1H), 2.04-1.92 (m,5H), 1.42-1.36 (m, 3H). LC-MS m/z calcd for C₃₂H₄₀N₄O₂, 512.3; found513.3 [M+H]⁺. HPLC purity 97.2%.

Example 124N-(2-aminophenyl)-4-(3-(4-(((2-(3,4-difluorophenyl)cyclopropyl)amino)methyl)piperidin-1-yl)propyl)benzamideTFA Salt

The compound was synthesized using I-124 following the procedure forexample 120. ¹HNMR (400 MHz, DMSO-d₆): δ 9.71 (bs, 1H), 9.35 (bs, 1H),9.01 (bs, 2H), 7.94 (d, 2H, J=7.6 Hz), 7.37 (d, 2H, J=7.6 Hz), 7.32-7.26(m, 1H), 7.18 (d, 1H, J=7.6 Hz), 7.08-6.99 (m, 2H), 6.86 (d, 2H, J=7.6Hz), 6.72-6.67 (m, 1H), 3.56-3.51 (m, 2H), 3.29-2.82 (m, 8H), 2.74-2.68(m, 2H), 2.14-1.72 (m, 6H), 1.49-1.31 (m, 3H). LC-MS m/z calcd forC₃₁H₃₆F₂N₄O, 518.3. found 519.6 [M+H]⁺. HPLC purity 99.6%.

Example 125N-(2-aminophenyl)-4-(3-(4-(((2-(4-(piperidine-1-carbonyl)phenyl)cyclopropyl)amino)methyl)piperidin-1-yl)propyl)benzamideTFA Salt

The compound was synthesized using I-125 following the procedure forexample 120. ¹HNMR (400 MHz, DMSO-d₆): δ 9.70 (bs, 1H), 8.96 (bs, 1H),8.90 (bs, 1H), 7.95 (bs, 1H), 7.94 (d, 2H, J=8.4 Hz), 7.37 (d, 2H, J=7.6Hz), 7.29 (d, 2H, J=8 Hz), 7.23 (d, 2H, J=8 Hz), 7.17 (d, 1H, J=7.6 Hz),7.01 (t, 1H, J=7.6 Hz), 6.85 (d, 1H, J=8 Hz), 6.73-6.65 (m, 1H),3.59-3.50 (m, 5H), 3.30-3.17 (m, 3H), 3.09-3.00 (m, 5H), 2.95-2.84 (m,2H), 2.77-2.67 (m, 2H), 2.05-1.90 (m, 5H), 1.55-1.32 (m, 9H). LC-MS m/zcalcd for C₃₇H₄₇N₅O₂, 593.4. found 594.4 [M+H]⁺. HPLC purity 99.9%.

Example 126N-(2-aminophenyl)-4-(3-(3-(((2-(4-fluorophenyl)cyclopropyl)amino)methyl)azetidin-1-yl)propyl)benzamideTFA Salt

Step-1: N-(2-aminophenyl)-4-(3-hydroxypropyl)benzamide-XCIII

To a stirred solution of 4-(3-hydroxypropyl)benzoic acid (XCII, 0.7 g,3.89 mmol) in dry dichloromethane (15 mL) was added benzene-1,2-diamine(1.26 g, 11.66 mmol), triethylamine (1.64 mL, 11.66 mmol) and cooled to0° C. Then T3P (1.48 mL, 4.66 mmol) was added and the resulting mixturewas stirred at room temperature for 3 h. After completion of thereaction, the mixture was quenched with ice water and extracted withdichloromethane. The organic layer was washed with water, brine, driedover sodium sulphate and concentrated under reduced pressure to affordthe crude compound which was purified by column chromatography usingethylacetate-hexane gradient to afford the titled product as sticky oil.(XCIII, 0.6 g, 57%). LC-MS m/z calcd for C₁₆H₁₈N₂O₂, 270.1; found 271.0[M+H]⁺.

Step-2: tert-butyl(2-(4-(3-hydroxypropyl)benzamido)phenyl)carbamate-XCIV

To a stirred solution of N-(2-aminophenyl)-4-(3-hydroxypropyl)benzamide(XCIII, 0.3 g, 0.90 mmol) in tetrahydrofuran-water mixture (1:1, 10 mL)was added sodium bicarbonate (0.227 g, 2.71 mmol) and Boc anhydride(0.23 mL, 1.08 mmol) at room temperature. After 1 h, the reactionmixture was diluted with ethyl acetate and was washed with water, brine,dried over sodium sulphate and concentrated under reduced pressure toget the crude product which was purified by column chromatography usingethylacetate-hexane gradient to afford the titled product as thick oil(XCIV, 0.25 g, 61%). LC-MS m/z calcd for C₂₁H₂₆N₂O₄, 370.1; found 371.0[M+H]⁺.

Step-3: N-(2-aminophenyl)-4-(3-bromopropyl)benzamide-XCV

To a stirred solution of tert-butyl(2-(4-(3-hydroxypropyl)benzamido)phenyl)carbamate (XCIV, 0.3 g, 0.90mmol) in dichloromethane (5 mL) was added triphenylphosphine (0.31 g,0.95 mmol) and tetrabromomethane (0.41 g, 1.09 mmol) at 0° C. After 16h, the reaction mixture was diluted with dichloromethane and was washedwith water, brine solution, dried over sodium sulphate and concentratedunder reduced pressure to get the crude product which was purified bycolumn chromatography using ethylacetate-hexane gradient to afford thetitled product as thick oil (XCV, 0.17 g, 70%). LC-MS m/z calcd forC₁₆H₁₇BrN₂O, 332.0; found 333.1 [M+H]⁺.

Step-4: tert-butyl (2-(4-(3-bromopropyl)benzamido)phenyl)carbamate-XCVI

To a stirred solution of N-(2-aminophenyl)-4-(3-bromopropyl)benzamide(XCV, 0.22 g, 0.66 mmol) in tetrahydrofuran-water mixture (1:1, 10 mL)was added sodium bicarbonate (0.16 g, 1.98 mmol) and Boc anhydride (0.17mL, 0.79 mmol) at room temperature. After 1 h, the reaction mixture wasdiluted with ethylacetate and was washed with water, brine, dried oversodium sulphate and concentrated under reduced pressure to get the crudeproduct which was purified by column chromatography usingethylacetate-hexane gradient to afford the titled product as thick oil(XCVI, 0.23 g, 82%). LC-MS m/z calcd for C₂₁H₂₅BrN₂O₃, 432.1; found433.0 [M+H]⁺.

Step-5:tert-butyl(2-(4-(3-(3-((2,2,2-trifluoro-N-(2-(4-fluorophenyl)cyclopropyl)acetamido)methyl)azetidin-1-yl)propyl)benzamido)phenyl)carbamate-XCVII

To a solution ofN-(azetidin-3-ylmethyl)-2,2,2-trifluoro-N-(2-(4-fluorophenyl)cyclopropyl)acetamidetrifluoroacetate salt (XCVI, 0.18 g, 0.54 mmol) in acetonitrile (5 mL)was added tert-butyl (2-(4-(3-bromopropyl)benzamido)phenyl)carbamate(0.28 g, 0.65 mmol) and N,N-diisopropylethylamine (0.29 mL, 1.61 mmol).Then the reaction mixture was heated at 60° C. for 16 h. Aftercompletion of reaction, the reaction was diluted with ethylacetate (50mL), washed with water, brine solution, dried over sodium sulfate andconcentrated under vacuum to get crude product which was purified bycolumn chromatography using methanol-dichloromethane gradient to affordthe titled product as brown colour sticky oil (XCVII, 0.13 g, 36%).LC-MS m/z calcd for C₃₆H₄₀F₄N₄O₄, 668.3; found 669.1 [M+H]⁺.

Step-6:N-(2-aminophenyl)-4-(3-(3-(((2-(4-fluorophenyl)cyclopropyl)amino)methyl)azetidin-1-yl)propyl)benzamideTFA Salt—Example 126

To a solution of tert-butyl(2-(4-(3-(3-((2,2,2-trifluoro-N-(2-(4-fluorophenyl)cyclopropyl)acetamido)methyl)azetidin-1-yl)propyl)benzamido)phenyl)carbamate (XCVII,0.17 g, 0.25 mmol) in methanol (5 mL) was added potassium carbonate(0.10 g, 0.76 mmol) at room temperature for 16 h. After completion ofreaction, the reaction was concentrated under vacuum. The residue wasdiluted with dichloromethane and cooled to 0° C. TFA (0.46 mL) was addedto it and stirred for 1 h at same temperature. The solvent wasconcentrated under reduced pressure to get the crude product which waspurified by reverse-phase HPLC using Chemsil C₁₈ (250 mm×4.6 mm×5mic)column with 0.1% TFA in water:ACN to afford the pure product as acolourless solid (Example 126, 0.04 g, 37%). ¹HNMR (400 MHz, DMSO-d₆): δ9.87 (bs, 1H), 9.65 (s, 1H), 9.01 (bs, 2H), 7.93 (d, 2H, J=8 Hz), 7.34(s, 2H, J=7.6 Hz), 7.25-7.19 (m, 2H), 7.16-7.10 (m, 3H), 6.99 (t, 1H,J=7.6 Hz), 6.81 (d, 1H, J=7.6 Hz), 6.65 (t, 1H, J=7.6 Hz), 4.18 (m, 1H),4.12-3.95 (m, 2H), 3.90-3.78 (m, 2H), 3.42-3.28 (m, 2H), 3.20-3.02 (m,4H), 2.95-2.80 (m, 1H), 2.72-2.62 (m, 1H), 1.80-1.68 (m, 2H), 1.42-1.35(m, 1H), 1.32-1.24 (m, 1H). LC-MS m/z calcd for C₂₉H₃₃FN₄O, 472.3; found473.3 [M+H]⁺. HPLC purity 99.8%.

Example 127N-(2-aminophenyl)-4-(3-(6-((2-phenylcyclopropyl)amino)-2-azaspiro[3.3]heptan-2-yl)propyl)benzamideTFA Salt

The compound was synthesized using I-127 following the procedure forexample 120. ¹HNMR (400 MHz, DMSO-d₆): δ 10.48 (bs, 1H), 9.69 (s, 1H),8.55 (bs, 2H), 7.93 (d, 2H, J=7.6 Hz), 7.40-7.28 (m, 4H), 7.25-7.14 (m,4H), 7.00 (t, 1H, J=7.6 Hz), 6.85 (d, 1H, J=7.6 Hz), 6.68 (t, 1H, J=7.2Hz), 4.38-4.4.26 (m, 1H), 3.75-3.62 (m, 1H), 3.38-3.15 (m, 4H),3.00-2.96 (m, 2H), 2.78-2.70 (m, 2H), 2.68-2.60 (m, 1H), 2.24-2.04 (m,3H), 2.00-1.88 (m, 2H), 1.70-1.55 (m, 2H), 1.45-1.32 (m, 1H). LC-MS m/zcalcd for C₃₁H₃₆N₄O, 480.3; found 481.3 [M+H]⁺. HPLC purity 99.6%.

Example 128N-(2-aminophenyl)-4-(3-(4-(((2-(1-isopropyl-1H-pyrazol-4-yl)cyclopropyl)amino)methyl)piperidin-1-yl)propyl)benzamideTFA Salt

The compound was synthesized using I-128 following the procedure forexample 120. ¹HNMR (400 MHz, DMSO-d₆): δ 9.73 (bs, 1H), 9.22 (bs, 1H),8.34 (bs, 2H), 7.94 (d, 2H, J=7.6 Hz), 7.61 (s, 1H), 7.37 (d, 2H, J=8Hz), 7.29 (s, 1H), 7.19 (d, 1H, J=7.6 Hz), 7.03 (t, 1H, J=7.6 Hz), 6.88(d, 1H, J=8 Hz), 6.73 (t, 1H, J=7.2 Hz), 4.42-4.35 (m, 1H), 3.55-3.52(m, 2H), 3.08-2.98 (m, 4H), 2.96-2.87 (m, 2H), 2.83-2.78 (m, 1H),2.75-2.68 (m, 2H), 2.23-2.19 (m, 1H), 2.06-1.90 (m, 5H), 1.46-1.40 (m,9H), 1.21-1.06 (m, 1H). LC-MS m/z calcd for C₃₁H₄₂N₆O, 514.3; found515.3 [M+H]⁺. HPLC purity 98.8%.

Example 129N-(2-aminophenyl)-4-(3-(4-(((2-(1-phenyl-1H-pyrazol-4-yl)cyclopropyl)amino)methyl)piperidin-1-yl)propyl)benzamideTFA Salt

The compound was synthesized using I-129 following the procedure forexample 120. ¹HNMR (400 MHz, DMSO-d₆): δ 9.70 (bs, 1H), 9.54 (bs, 1H),9.09 (bs, 2H), 8.37 (s, 1H), 7.94 (d, 2H, J=8 Hz), 7.73 (d, 2H, J=8 Hz),7.65 (s, 1H), 7.47 (t, 2H, J=8 Hz), 7.36 (d, 2H, J=8 Hz), 7.28 (t, 1H,J=7.6 Hz), 7.18 (d, 1H, J=8 Hz), 7.03-6.98 (m, 1H), 6.85 (d, 1H, J=8Hz), 6.71-6.66 (m, 1H), 3.58-3.51 (m, 2H), 3.10-3.02 (m, 4H), 2.95-2.84(m, 3H), 2.74-2.68 (m, 2H), 2.38-2.32 (m, 1H), 2.03-1.94 (m, 5H),1.50-1.41 (m, 3H), 1.25-1.19 (m, 1H). LC-MS m/z calcd for C₃₄H₄₀N60,548.3; found 549.3 [M+H]⁺. HPLC purity 99%.

Example 130N-(2-aminophenyl)-4-(3-(4-(((2-(2-methylthiazol-5-yl)cyclopropyl)amino)methyl)piperidin-1-yl)propyl)benzamideTFA Salt

The compound was synthesized using I-130 following the procedure forexample 120. LC-MS m/z calcd for C₂₉H₃₇N₅OS, 503.7; found 504.7 [M+H]⁺.

Example 131N-(2-aminophenyl)-4-(3-(4-(((2-(pyridin-3-yl)cyclopropyl)amino)methyl)piperidin-1-yl)propyl)benzamideTFA Salt

The compound was synthesized using I-131 following the procedure forexample 120. LC-MS m/z calcd for C₃₀H₃₇N₅O, 483.6; found 484.6 [M+H]⁺.

Example 132N-(2-amino-5-fluorophenyl)-4-(3-(4-(((2-(4-fluorophenyl)cyclopropyl)amino)methyl)piperidin-1-yl)propyl)benzamideTFA Salt

The compound was synthesized using I-122 following the procedure forexample 120. ¹HNMR (400 MHz, DMSO-d₆): δ 9.53 (s, 1H), 9.42 (bs, 1H),9.04 (bs, 2H), 7.95 (d, 2H, J=8.0 Hz), 7.34 (d, 2H, J=8.0 Hz), 7.23-7.19(m, 2H), 7.14-7.06 (m, 3H), 6.55-6.51 (m, 1H), 6.37-6.32 (m, 1H),3.58-3.50 (m, 2H), 3.30-3.24 (m, 1H), 3.22-3.14 (m, 1H), 3.08-2.98 (m,3H), 2.95-2.81 (m, 3H), 2.74-2.64 (m, 2H), 2.06-1.85 (m, 5H), 1.46-1.36(m, 3H), 1.29-1.24 (m, 1H). LC-MS m/z calcd for C₃₁H₃₆F₂N₄O, 518.3;found 519.2 [M+H]⁺. HPLC purity 98.6%.

Example 133N-(2-aminophenyl)-4-(3-oxo-3-(4-((2-phenylcyclopropyl)amino)piperidin-1-yl)propyl)benzamideTFA Salt

The compound was synthesized using I-133 following the procedure forexample 120. ¹HNMR (400 MHz, DMSO-d₆): δ 9.69 (s, 1H), 8.99 (bs, 2H),7.88 (d, 2H, J=8 Hz), 7.36 (d, 2H, J=8 Hz), 7.31-7.27 (m, 2H), 7.26-7.16(m, 4H), 7.05-7.00 (m, 1H), 6.88-6.86 (m, 1H), 6.75-6.72 (m, 1H),4.48-4.41 (m, 1H), 4.03-3.96 (m, 1H), 3.52-3.42 (m, 1H), 3.04-2.97 (m,2H), 2.90-2.82 (m, 2H), 2.72-2.65 (m, 2H), 2.60-2.52 (m, 1H), 2.42-2.34(m, 1H), 2.06-2.01 (m, 2H), 1.42-1.30 (m, 4H). LC-MS m/z calcd forC₃₀H₃₄N₄O₂ 482.3. found 483.2 [M+H]⁺. HPLC purity 94.3%.

Example 134N-(2-aminophenyl)-4-(3-oxo-3-(4-(((2-phenylcyclopropyl)amino)methyl)piperidin-1-yl)propyl)benzamideTFA Salt

The compound was synthesized using I-134 following the procedure forexample 120. ¹HNMR (400 MHz, DMSO-d₆): δ 9.70 (bs, 1H), 8.80 (bs, 2H),7.88 (d, 2H, J=8 Hz), 7.36 (d, 2H, J=8 Hz), 7.32-7.24 (m, 2H), 7.22-7.12(m, 4H), 7.05-6.98 (m, 1H), 6.85-6.83 (m, 1H), 6.75-6.70 (m, 1H),4.37-4.34 (m, 1H), 3.89-3.84 (m, 1H), 3.02-2.82 (m, 3H), 2.80-2.75 (m,2H), 2.68-2.62 (m, 2H), 2.46-2.37 (m, 2H), 1.92-1.82 (m, 1H), 1.74-1.64(m, 2H), 1.45-1.42 (m, 1H), 1.33-1.20 (m, 2H), 1.07-0.98 (m, 2H). LC-MSm/z calcd for C₃₁H₃₆N₄O₂, 496.3; found 497.4 [M+H]⁺. HPLC purity 96.2%.

Example 135N-(2-aminophenyl)-4-(3-(4-(((2-(3,4-difluorophenyl)cyclopropyl)amino)methyl)-1H-imidazol-1-yl)propyl)benzamideTFA Salt

The compound was synthesized using I-135 following the procedure forexample 120. ¹HNMR (400 MHz, DMSO-d₆): δ 9.75 (bs, 1H), 8.16 (s, 1H),7.92 (d, 2H, J=7.6 Hz), 7.42 (s, 1H), 7.37-7.28 (m, 3H), 7.22-7.16 (m,2H), 7.04 (t, 1H, J=7.6 Hz), 7.02-6.96 (m, 1H), 6.90 (t, 1H, J=8.0 Hz),6.76 (t, 1H, J=7.6 Hz), 4.22 (s, 2H), 4.06-4.00 (m, 2H), 2.93-2.90 (m,1H), 2.65-2.60 (m, 2H), 2.37-2.30 (m, 1H), 2.08-2.00 (m, 2H), 1.42-1.38(m, 1H), 1.33-1.28 (m, 1H). LC-MS m/z calcd for C₂₉H₂₉F₂N₅O, 501.2;found 502.2 [M+H]⁺. HPLC purity 99.5%.

Example 136N-(2-aminophenyl)-4-(3-(4-(((2-phenylcyclopropyl)amino)methyl)-1H-imidazol-1-yl)propyl)benzamide TFA Salt

The compound was synthesized using I-136 following the procedure forexample 120. ¹HNMR (400 MHz, DMSO-d₆): δ 9.73 (bs, 1H), 9.00 (bs, 1H),8.09 (s, 1H), 7.92 (d, 2H, J=7.6 Hz), 7.39 (s, 1H), 7.31 (d, 2H, J=7.6Hz), 7.28-7.24 (m, 2H), 7.20-7.16 (m, 2H), 7.09 (d, 2H, J=7.6 Hz), 7.03(t, 1H, J=7.6 Hz), 6.88 (d, 1H, J=8 Hz), 6.74 (t, 1H, J=7.2 Hz),4.23-4.18 (m, 2H), 4.04-4.00 (m, 2H), 2.94-2.88 (m, 1H), 2.64-2.57 (m,2H), 2.38-2.30 (m, 1H), 2.09-1.99 (m, 2H), 1.43-1.37 (m, 1H), 1.30-1.21(m, 1H). LC-MS m/z calcd for C₂₉H₃₁N₅O, 465.3; found 466.3 [M+H]⁺. HPLCpurity 99.8%.

Example 137N-(2-aminophenyl)-4-(3-(4-(((2-phenylcyclopropyl)amino)methyl)-1H-1,2,3-triazol-1-yl)propyl)benzamideTFA Salt

The compound was synthesized using I-137 following the procedure forexample 120. ¹HNMR (400 MHz, DMSO-d₆): δ 9.71 (bs, 1H), 9.47 (bs, 2H),8.18 (s, 1H), 7.92 (d, 2H, J=7.6 Hz), 7.32 (d, 2H, J=7.6 Hz), 7.29-7.24(m, 2H), 7.20-7.16 (m, 2H), 7.11 (d, 2H, J=7.6 Hz), 7.02 (t, 1H, J=7.6Hz), 6.86 (d, 1H, J=8 Hz), 6.71 (t, 1H, J=7.2 Hz), 4.23-4.18 (m, 2H),4.04-4.00 (m, 2H), 2.94-2.88 (m, 1H), 2.64-2.57 (m, 2H), 2.38-2.30 (m,1H), 2.09-1.99 (m, 2H), 1.43-1.37 (m, 1H), 1.30-1.21 (m, 1H). LC-MS m/zcalcd for C₂₈H₃₀N₆O, 466.2; found 467.3 [M+H]⁺. HPLC purity 98.7%.

Example 138N-(2-aminophenyl)-4-(3-(4-(((2-phenylcyclopropyl)amino)methyl)-1H-pyrazol-1-yl)propyl)benzamideTFA Salt

The compound was synthesized using I-138 following the procedure forexample 120. ¹HNMR (400 MHz, DMSO-d₆): δ 9.69 (bs, 1H), 9.09 (bs, 1H),9.05 (bs, 1H), 7.91 (d, 2H, J=7.6 Hz), 7.78 (s, 1H), 7.53 (s, 1H),7.32-7.25 (m, 4H), 7.20 (t, 2H, J=7.6 Hz), 7.12 (d, 2H, J=7.6 Hz), 7.01(t, 1H, J=7.6 Hz), 6.86 (d, 1H, J=8 Hz), 6.70 (t, 1H, J=7.2 Hz),4.42-4.17 (m, 2H), 4.10 (t, 2H, J=6.8 Hz), 2.94-2.86 (m, 1H), 2.65-2.57(m, 2H), 2.40-2.33 (m, 1H), 2.11-2.01 (m, 2H), 1.44-1.37 (m, 1H),1.32-1.25 (m, 1H). LC-MS m/z calcd for C₂₉H₃₁N₅O, 465.3; found 466.3[M+H]⁺. HPLC purity 99%.

Example 139N-(2-aminophenyl)-4-(2-(4-(((2-phenylcyclopropyl)amino)methyl)piperidin-1-yl)ethyl)benzamideTFA Salt

The compound was synthesized using I-139 following the procedure forexample 120. ¹HNMR (400 MHz, DMSO-d₆): δ 9.64 (bs, 1H), 9.36 (bs, 1H),8.89 (bs, 2H), 7.96 (d, 2H, J=8.0 Hz), 7.40 (d, 2H, J=8.0 Hz), 7.34-7.28(m, 2H), 7.23 (d, 1H, J=7.6 Hz), 7.21-7.12 (m, 3H), 6.98 (t, 1H, J=7.6Hz), 6.80 (d, 1H, J=8.0 Hz), 6.62 (d, 1H, J=8.0 Hz), 3.68-3.60 (m, 2H),3.36-3.28 (m, 3H), 3.10-3.02 (m, 4H), 3.01-2.92 (m, 3H), 2.04-1.96 (m,2H), 1.95-1.88 (m, 1H), 1.50-1.40 (m, 3H), 1.34-1.28 (m, 1H). LC-MS m/zcalcd for C₃₀H₃₆N₄O, 468.6; found 469.6 [M+H]⁺. HPLC purity 99%.

Example 140N-(2-aminophenyl)-4-((4-((((1R,2S)-2-phenylcyclopropyl)amino)methyl)piperidin-1-yl)methyl)benzamideTFA Salt

The compound was synthesized using I-140 following the procedure forexample 120. ¹HNMR (400 MHz, DMSO-d₆): δ 9.75 (s, 1H), 9.64 (bs, 1H),8.94 (bs, 2H), 8.25 (d, 2H, J=8.0 Hz), 7.62 (d, 2H, J=8 Hz), 7.29 (t,2H, J=7.2 Hz), 7.25-7.10 (m, 3H), 6.97 (t, 1H, J=7.6 Hz), 6.81 (d, 1H,J=8.0 Hz), 6.72 (t, 1H, J=6.8 Hz), 4.29 (s, 2H), 3.46-3.34 (m, 2H),3.26-3.10 (m, 1H), 3.06-2.86 (m, 5H), 2.02-1.78 (m, 3H), 1.52-1.34 (m,3H), 1.32-1.24 (m, 1H). LC-MS m/z calcd for C₂₉H₃₄N₄O, 454.2; found455.2 [M+H]⁺. HPLC purity 96.5%.

Example 141N-(2-aminophenyl)-4-((4-(((2-(4-(1-methyl-6-oxo-1,6-dihydropyridin-3-yl)phenyl)cyclopropyl)amino)methyl)piperidin-1-yl)methyl)benzamideTFA Salt

The compound was synthesized using I-141 following the procedure forexample 120. ¹HNMR (400 MHz, DMSO-d₆): δ 9.86 (bs, 2H), 9.09 (bs, 2H),8.08-8.60 (m, 3H), 7.79 (dd, J=9.2, 2 Hz, 1H), 7.62 (d, J=8.0 Hz, 2H),7.49 (d, J=8.0 Hz, 2H), 7.22-7.19 (m, 3H), 7.04 (t, J=7.6 Hz, 1H), 6.89(d, J=8.0 Hz, 1H), 6.74 (d, J=7.2 Hz, 1H), 6.46 (d, J=9.2 Hz, 1H), 4.37(s, 2H), 3.49 (s, 3H), 3.42-3.39 (m, 2H), 3.28-3.10 (m, 1H), 3.05-2.94(m, 5H), 2.02-1.82 (m, 3H), 1.51-1.37 (m, 3H), 1.34-1.27 (m, 1H). LC-MSm/z calcd for C₃₅H₃₉N₅O₂, 561.3; found 560.6[M−H]⁺. HPLC purity 99.9%.

Example 142N-(2-aminophenyl)-4-((4-(((2-(4-(1-methyl-1H-pyrazol-4-yl)phenyl)cyclopropyl)amino)methyl)piperidin-1-yl)methyl)benzamideTFA Salt

The compound was synthesized using I-142 following the procedure forexample 120. ¹HNMR (400 MHz, DMSO-d₆): δ 9.77 (bs, 1H), 8.89 (bs, 1H),8.08 (bs, 2H), 8.08 (bs, 3H), 7.81 (s, 1H), 7.61 (d, J=7.6 Hz, 2H), 7.47(d, J=8 Hz, 2H), 7.17-7.13 (m, 3H), 7.04-6.98 (m, 1H), 6.85-6.80 (m,1H), 6.68-6.62 (m, 1H), 4.46-4.32 (m, 4H), 3.83 (s, 3H), 3.43-3.38 (m,2H), 3.25-3.12 (m, 2H), 3.06-2.96 (m, 5H), 1.98-1.84 (m, 3H), 1.46-1.36(m, 3H), 1.30-1.26 (m, 1H). LC-MS m/z calcd for C₃₅H₃₉N₅O₂, 534.3; found535.2 [M+H]⁺. HPLC purity 99.8%.

Example 143N-(2-aminophenyl)-4-((4-(((2-(4-(3,5-dimethylisoxazol-4-yl)phenyl)cyclopropyl)amino)methyl)piperidin-1-yl)methyl)benzamideTFA Salt

The compound was synthesized using I-143 following the procedure forexample 120. ¹HNMR (400 MHz, DMSO-d₆): δ 9.76 (bs, 1H), 9.69 (bs, 1H),9.03 (bs, 1H), 8.97 (bs, 1H), 8.07 (d, J=7.2 Hz, 2H), 7.61 (d, J=7.2 Hz,2H), 7.34-7.25 (m, 4H), 7.16 (d, J=7.6 Hz, 1H), 7.00 (t, J=7.6 Hz, 1H),6.82 (d, J=8 Hz, 1H), 6.65 (t, J=7.2 Hz, 1H), 4.46-4.32 (m, 2H),3.45-3.37 (m, 2H), 3.26-3.13 (m, 1H), 3.08-2.91 (m, 5H), 2.36 (s, 3H),2.18 (s, 3H), 2.00-1.82 (m, 3H), 1.51-1.31 (m, 4H). LC-MS m/z calcd forC₃₅H₃₉N₅O₂, 549.3; found 550.3 [M+H]⁺. HPLC purity 99.6%.

Example 144N-(2-aminophenyl)-4-((4-(((2-(4-(pyrimidin-5-yl)phenyl)cyclopropyl)amino)methyl)piperidin-1-yl)methyl)benzamideTFA Salt

The compound was synthesized using I-145 following the procedure forexample 120. ¹HNMR (400 MHz, DMSO-d₆): δ 9.77 (bs, 1H), 9.66 (bs, 1H),9.16 (s, 1H), 9.12 (s, 2H), 9.02 (bs, 2H), 8.07 (d, J=7.2 Hz, 2H), 7.76(d, J=8 Hz, 2H), 7.62 (d, J=8 Hz, 2H), 7.34 (d, J=8 Hz, 2H), 7.16 (d,J=7.6 Hz, 1H), 7.00 (t, J=7.6 Hz, 1H), 6.82 (d, J=7.6 Hz, 1H), 6.65 (t,J=7.6 Hz, 1H), 4.37 (s, 2H), 3.46-3.37 (m, 2H), 3.27-3.12 (m, 1H),3.10-2.90 (m, 5H), 2.03-1.82 (m, 3H), 1.56-1.37 (m, 4H). LC-MS m/z calcdfor C₃₃H₃₆N₆O, 532.3; found 533.6 [M+H]⁺. HPLC purity 99.9%.

Example 145N-(2-aminophenyl)-4-((4-(((2-phenylcyclopropyl)amino)methyl)-1H-pyrazol-1-yl)methyl)benzamideTFA Salt

The compound was synthesized using I-145 following the procedure forexample 120. ¹HNMR (400 MHz, DMSO-d₆): δ 9.65 (bs, 1H), 9.02 (bs, 2H),7.93 (d, 2H, J=7.6 Hz), 7.89 (s, 1H), 7.56 (s, 1H), 7.34-7.25 (m, 4H),7.23-7.19 (m, 1H), 7.18-7.10 (m, 3H), 6.98 (t, 1H, J=7.6 Hz), 6.81 (d,1H, J=8 Hz), 6.63 (t, 1H, J=7.2 Hz), 5.41 (s, 2H), 4.19 (s, 2H),2.94-2.86 (m, 1H), 2.40-2.31 (m, 1H), 1.43-1.37 (m, 1H), 1.32-1.22 (m,1H). LC-MS m/z calcd for C₂₇H₂₇N₅O, 437.2; found 438.3 [M+H]⁺. HPLCpurity 98.7%.

Example 146N-(2-aminophenyl)-4-((4-(((2-phenylcyclopropyl)amino)methyl)-1H-1,2,3-triazol-1-yl)methyl)benzamideTFA Salt

The compound was synthesized using I-146 following the procedure forexample 120. ¹HNMR (400 MHz, DMSO-d₆): δ 9.72 (bs, 1H), 9.44 (bs, 2H),8.24 (s, 1H), 7.97 (d, 2H, J=7.6 Hz), 7.42 (d, 2H, J=8 Hz), 7.31-7.26(m, 2H), 7.23-7.15 (m, 2H), 7.11 (d, 2H, J=7.2 Hz), 7.00 (t, 1H, J=7.6Hz), 6.84 (d, 1H, J=8 Hz), 6.67 (t, 1H, J=7.2 Hz), 5.73 (s, 2H), 4.43(s, 2H), 2.99-2.98 (m, 1H), 2.40-2.37 (m, 1H), 1.44-1.37 (m, 1H),1.30-1.24 (m, 1H). LC-MS m/z calcd for C₂₆H₂₆N₆O, 438.2; found 439.5[M+H]⁺. HPLC purity 98.9%.

Example 147N-(2-aminophenyl)-4-(2-(4-(((2-(4-fluorophenyl)cyclopropyl)amino)methyl)piperidin-1-yl)-2-oxoethyl)benzamideTFA Salt

The compound was synthesized using I-147 following the procedure forexample 120. ¹HNMR (400 MHz, DMSO-d₆): δ 9.73 (s, 1H), 8.793 (bs, 2H),7.91 (d, 2H, J=8.0 Hz), 7.35 (d, 2H, J=8.4 Hz), 7.23-7.19 (m, 3H),7.14-7.10 (m, 2H), 7.04-7.01 (m, 1H), 6.89-6.87 (m, 1H), 6.76-6.70 (m,1H), 4.38-4.35 (m, 1H), 3.99-3.96 (m, 1H), 3.79 (s, 2H), 3.05-2.92 (m,4H), 2.65-2.55 (m, 1H), 2.48-2.42 (m, 1H), 1.92-1.85 (m, 1H), 1.76-1.67(m, 2H), 1.47-1.39 (m, 1H), 1.32-1.26 (m, 1H), 1.05-0.97 (m, 2H), LC-MSm/z calcd for C₃₀H₃₃FN₄O₂, 500.1; found 501.2 [M+H]⁺. HPLC purity 99.9%.

Example 148N-(2-aminophenyl)-4-(2-((2-(4-fluorophenyl)cyclopropyl)amino)ethoxy)benzamide TFA Salt

The compound was synthesized using I-148 following the procedure forexample 120. ¹HNMR (400 MHz, DMSO-d₆): δ 9.69 (s, 1H), 9.18 (bs, 2H),7.98 (d, 2H, J=8.8 Hz), 7.21-7.19 (m, 3H), 7.14-7.01 (m, 5H), 6.92-6.88(m, 1H), 6.78-6.74 (m, 1H), 4.34-4.29 (m, 3H), 3.59-3.51 (m, 2H),3.09-3.02 (m, 1H), 1.48-1.43 (m, 1H), 1.34-1.29 (m, 1H). LC-MS m/z calcdfor C₂₄H₂₄FN₃O₂, 405.4; found 406.2 [M+H]⁺. HPLC purity 99.7%.

Example 149N-(2-aminophenyl)-6-(2-(4-(((2-(4-fluorophenyl)cyclopropyl)amino)methyl)piperidin-1-yl)ethoxy)nicotinamideTFA Salt

The compound was synthesized using I-149 following the procedure forexample 120. ¹HNMR (400 MHz, DMSO-d₆): δ 9.48 (s, 1H), 9.29 (bs, 1H),8.98 (bs, 2H), 8.49 (s, 1H), 8.06 (d, J=7.6 Hz, 1H), 7.25-7.20 (m, 2H),7.16-7.07 (m, 3H), 6.98 (t, J=7.2 Hz, 1H), 6.80 (d, J=7.6 Hz, 1H), 6.61(t, J=7.2 Hz, 1H), 6.51 (d, J=9.6 Hz, 1H), 4.40-4.30 (m, 2H), 3.70-3.65(m, 2H), 3.46-3.39 (m, 2H), 3.30-3.25 (m, 1H), 3.05-2.95 (m, 5H),2.03-1.95 (m, 3H), 1.49-1.39 (m, 3H), 1.31-1.26 (m, 1H). LC-MS m/z calcdfor C₂₉H₃₄FN₅O₂, 503.2; found 504.3[M+H]⁺. HPLC purity 99.6%.

Example 150N-(-2-aminophenyl)-2-((2-4(((2-(4-flurophenyl)cyclopropyl)amino)methyl)piperdine-1-yl)ethyl)amino)pyrimidine-5-carboxamideTFA Salt

The compound was synthesized using I-150 following the procedure forexample 120. ¹HNMR (400 MHz, DMSO-d₆): δ 9.68 (bs, 1H), 9.35 (bs, 1H),9.08 (bs, 2H), 8.88 (s, 2H), 7.98-7.93 (m, 1H), 7.24-7.10 (m, 5H), 7.03(t, 1H, J=7.2 Hz), 6.88 (d, 1H, J=8 Hz), 6.73 (t, 1H, J=7.6 Hz),3.76-3.60 (m, 4H), 3.34-3.21 (m, 3H), 3.05-2.92 (m, 4H), 2.46-2.41 (m,1H), 2.01-1.92 (m, 3H), 1.49-1.40 (m, 3H), 1.30-1.24 (m, 1H). LC-MS m/zcalcd for C₂₈H₃₄FN₇O, 503.2; found 504.3[M+H]⁺. HPLC purity 99.8%.

Example 151N-(2-aminophenyl)-5-((2-(4-fluorophenyl)cyclopropyl)glycyl)-4,5,6,7-tetrahydrothieno[3,2-c]pyridine-2-carboxamideTFA Salt

The compound was synthesized using I-151 following the procedure forexample 120. ¹HNMR (400 MHz, DMSO-d₆): 9.65 (s, 1H), 9.23 (s, 2H),7.73-7.71 (m, 1H), 7.22-7.20 (m, 2H), 7.13-7.09 (m, 3H), 6.98 (bs, 1H),6.80 (bs, 1H), 6.63 (bs, 1H), 4.62 (s, 1H), 4.55 (s, 1H), 4.37-4.35 (m,2H), 3.70 (s, 2H), 2.97 (s, 2H), 2.85 (s, 2H), 1.48 (bs, 1H), 1.28-1.26(m, 1H). LC-MS m/z calcd [M+H]⁺ 464.1. found 465.0. HPLC purity 99.0%.

Example 152N-(2-aminophenyl)-2-(2-((2-(4-fluorophenyl)cyclopropyl)amino)acetyl)-1,2,3,4-tetrahydroisoquinoline-7-carboxamideTFA Salt

The compound was synthesized using I-152 following the procedure forexample 120. ¹HNMR (400 MHz, DMSO-d₆): δ 9.66 (bs, 1H), 9.26 (bs, 2H),7.86-7.79 (m, 2H), 7.34-7.32 (d, 1H, J=8.0 Hz), 7.25-7.15 (m, 3H),7.14-7.07 (m, 2H), 7.02-6.98 (m, 1H), 6.85-6.81 (m, 1H), 6.71-6.64 (m,1H), 4.74-4.70 (m, 2H), 4.35 (s, 2H), 3.76-3.74 (m, 3H), 3.02-2.96 (m,1H), 2.90-2.82 (m, 2H), 1.52-1.48 (m, 1H), 1.32-1.26 (m, 1H). LC-MS m/zcalcd for C₂₇H₂₇FN₄O₂, 458.2; found 459.2 [M+H]⁺. HPLC purity 99.2%.

Example 153N-(2-aminophenyl)-2-(3-(4-(((2-phenylcyclopropyl)amino)methyl)piperidin-1-yl)propyl)oxazole-4-carboxamideTFA Salt

The compound was synthesized using I-153 following the procedure forexample 120. ¹HNMR (400 MHz, DMSO-d₆): δ 9.36 (bs, 2H), 8.94 (bs, 2H),8.67 (s, 1H), 7.32-7.26 (m, 3H), 7.23-7.15 (m, 3H), 6.98 (t, J=7.6 Hz,1H), 6.83 (d, J=8 Hz, 1H), 6.66 (t, J=7.2 Hz, 1H), 3.60-3.54 (m, 2H),3.23-3.14 (m, 3H), 3.07-2.90 (m, 7H), 2.15-2.11 (m, 2H), 2.00-1.94 (m,3H), 1.49-1.40 (m, 3H), 1.32-1.26 (m, 1H). LC-MS m/z calcd forC₂₈H₃₅N₅O₂, 473.3; found 474.3 [M+H]⁺. HPLC purity 99.8%.

Example 154N-(2-aminophenyl)-2-(3-(4-(((2-phenylcyclopropyl)amino)methyl)piperidin-1-yl)propyl)thiazole-5-carboxamideTFA Salt

The compound was synthesized using I-154 following the procedure forexample 120. ¹HNMR (400 MHz, DMSO-d₆): δ 9.87 (bs, 1H), 9.35 (bs, 1H),9.00 (bs, 2H), 8.46 (s, 1H), 7.32-7.26 (m, 2H), 7.23-7.09 (m, 4H), 7.02(t, 1H, J=7.6 Hz), 6.83 (d, 1H, J=8 Hz), 6.66 (t, 1H, J=7.2 Hz),3.59-3.52 (m, 2H), 3.28-2.88 (m, 9H), 2.46-2.42 (m, 1H), 2.18-2.11 (m,2H), 2.00-1.94 (m, 3H), 1.49-1.39 (m, 3H), 1.32-1.22 (m, 1H). LC-MS m/zcalcd for C₂₈H₃₅N₅OS, 489.3; found 490.3 [M+H]⁺. HPLC purity 99.8%.

Example 155N-(2-aminophenyl)-4-((2-((2-(4-fluorophenyl)cyclopropyl)amino)acetamido)methyl)benzamideTFA Salt

The compound was synthesized using I-155 following the procedure forexample 120. ¹HNMR (400 MHz, DMSO-d₆): δ 9.70 (s, 1H), 9.30 (bs, 2H),8.97 (s, 1H), 7.94 (d, 2H, J=8 Hz), 7.39 (d, 2H, J=8 Hz), 7.22-7.18 (m,3H), 7.13-7.09 (m, 2H), 7.03-6.99 (m, 1H), 6.85 (d, 1H, J=7.2 Hz), 4.44(d, 2H, J=6 Hz), 3.98-3.74 (m, 5H), 2.92 (m, 1H), 1.47-1.45 (m, 1H),1.30-1.22 (m, 1H). LC-MS m/z calcd for C₂₅H₂₅FN₄O₂, 432.2; found 433.0[M+H]⁺. HPLC purity 99.8%.

Example 156E)-N-(2-aminophenyl)-4-(3-(4-(((2-(4-fluorophenyl)cyclopropyl)amino)methyl)piperidin-1-yl)-3-oxoprop-1-en-1-yl)benzamideTFA Salt

The compound was synthesized using I-156 following the procedure forexample 120. ¹HNMR (400 MHz, DMSO-d₆): δ 9.81 (s, 1H), 8.85 (bs, 2H),8.00 (d, 2H, J=7.6 Hz), 7.85 (d, 2H, J=8 Hz), 7.53 (d, 1H, J=15.6 Hz),7.40 (d, 1H, J=15.6 Hz), 7.25-7.19 (m, 3H), 7.16-7.11 (m, 2H), 7.05-7.02(m, 1H), 6.89-6.87 (m, 1H), 6.75-6.69 (m, 1H), 4.52-4.28 (m, 2H),3.17-2.92 (m, 4H), 2.76-2.63 (m, 1H), 2.48-2.45 (m, 1H), 2.03-1.92 (m,1H), 1.87-1.76 (m, 2H), 1.47-1.43 (m, 1H), 1.32-1.16 (m, 3H). LC-MS m/zcalcd for C₃₁H₃₃FN₄O₂, 512.6; found 513.2 [M+H]⁺. HPLC purity 99.7%.

Example 157(E)-N-(2-aminophenyl)-4-(3-(3-(((2-(4-fluorophenyl)cyclopropyl)amino)methyl)azetidin-1-yl)-3-oxoprop-1-en-1-yl)benzamideTFA Salt

The compound was synthesized using I-157 following the procedure forexample 120. ¹HNMR (400 MHz, DMSO-d₆): δ 9.80 (bs, 1H), 8.95 (bs, 2H),8.00 (d, J=8 Hz, 2H), 7.79 (d, J=8 Hz, 2H), 7.50 (d, J=15.6 Hz, 1H),7.26-7.21 (m, 5H), 7.05-7.00 (m, 1H), 6.90-6.85 (m, 1H), 6.79 (d, J=16Hz, 1H), 6.75-6.67 (m, 1H), 4.47-4.42 (m, 1H), 4.10-4.03 (m, 2H),3.82-3.77 (m, 1H), 3.47-3.38 (m, 2H), 3.03-2.92 (m, 2H), 1.47-1.40 (m,1H), 1.33-1.27 (m, 1H). LC-MS m/z calcd for C₂₉H₂₉FN₄O₂, 484.2; found485.2 [M+H]⁺. HPLC purity 99.6%.

Example 158N-(4-((2-aminophenyl)carbamoyl)benzyl)-4-(((2-(4-fluorophenyl)cyclopropyl)amino)methyl)piperidine-1-carboxamideTFA Salt

The compound was synthesized using I-158 following the procedure forexample 120. ¹HNMR (400 MHz, DMSO-d₆): δ 9.75 (s, 1H), 8.82 (bs, 2H),7.91 (d, 2H, J=7.6 Hz), 7.35 (d, 1H, J=8.0 Hz), 7.26-7.18 (m, 3H),7.16-7.08 (m, 3H), 7.08-7.02 (m, 1H), 6.94-6.88 (m, 1H), 6.79-6.75 (m,1H), 4.32-4.28 (m, 2H), 4.05-3.94 (m, 2H), 3.07-2.91 (m, 3H), 2.76-2.62(m, 2H), 2.48-2.43 (bs, 1H), 1.90-1.81 (m, 1H), 1.74-1.63 (m, 2H),1.46-1.41 (m, 1H), 1.30-1.25 (m, 1H), 1.15-1.00 (m, 2H). LC-MS m/z calcdfor C₃₀H₃₄FN₅O₂, 515.2; found 516.3 [M+H]⁺. HPLC purity 99.9%.

Example 159N-(2-aminophenyl)-4-(3-(2-oxo-4-(((2-phenylcyclopropyl)amino)methyl)piperidin-1-yl)propyl)benzamide TFA Salt

The compound was synthesized using I-159 following the procedure forexample 120. LC-MS m/z calcd for C₃₁H₃₆N₄O₂, 496.6; found 497.6 [M+H]⁺.

Example 160N-(2-aminophenyl)-4-((4-(((2-phenylcyclopropyl)amino)methyl)piperidin-1-yl)sulfonyl)benzamideTFA Salt

The compound was synthesized using I-160 following the procedure forexample 120. ¹HNMR (400 MHz, DMSO-d₆): δ 9.88 (bs, 1H), 8.73 (bs, 2H),8.19 (d, 2H, J=8.0 Hz), 7.85 (d, 2H, J=7.6 Hz), 7.31-7.24 (m, 2H),7.22-7.11 (m, 4H), 7.02-6.96 (m, 1H), 6.82-6.77 (m, 1H), 6.63-6.59 (m,1H), 3.72-3.67 (m, 2H), 3.02-2.92 (m, 4H), 2.38-2.32 (m, 1H), 2.28-2.24(m, 1H), 1.84-1.77 (m, 2H), 1.68-1.61 (m, 1H), 1.43-1.38 (m, 1H),1.34-1.21 (m, 3H). LC-MS m/z calcd for C₂₈H₃₂N₄O₃S, 504.2; found 505.3[M+H]⁺. HPLC purity 99.4%.

Example 161N-(2-aminophenyl)-4-(((4-(((2-phenylcyclopropyl)amino)methyl)piperidin-1-yl)sulfonyl)methyl)benzamide TFA Salt

The compound was synthesized using I-161 following the procedure forexample 120. ¹HNMR (400 MHz, DMSO-d₆): δ 9.83 (bs, 1H), 8.88 (bs, 2H),7.98 (d, 2H, J=8.0 Hz), 7.52 (d, 2H, J=7.6 Hz), 7.32-7.26 (m, 2H),7.23-7.14 (m, 4H), 7.07-7.03 (m, 1H), 6.92-6.88 (m, 1H), 6.78-6.74 (m,1H), 3.62-3.56 (m, 2H), 3.05-2.94 (m, 3H), 2.79-2.68 (m, 2H), 2.43-2.39(m, 1H), 1.80-1.70 (m, 3H), 1.46-1.42 (m, 1H), 1.31-1.20 (m, 5H). LC-MSm/z calcd for C₂₉H₃₄N₄O₃S, 518.2; found 519.2 [M+H]⁺.

Example 162N-(2-aminophenyl)-4-(2-((4-(((2-phenylcyclopropyl)amino)methyl)piperidin-1-yl)sulfonyl)ethyl)benzamide TFA

The compound was synthesized using I-162 following the procedure forexample 120. ¹HNMR (400 MHz, DMSO-d₆): δ 9.73 (bs, 1H), 8.85 (bs, 2H),7.92 (d, 2H, J=8.0 Hz), 7.43 (d, 2H, J=8 Hz), 7.31-7.26 (m, 2H),7.22-7.14 (m, 4H), 7.04-7.00 (m, 1H), 6.89-6.85 (m, 1H), 6.74-6.68 (m,1H), 3.65-3.60 (m, 2H), 3.40-2.35 (m, 2H), 3.07-3.00 (m, 4H), 2.98-2.93(m, 1H), 2.84-2.76 (m, 2H), 2.43-2.40 (m, 1H), 1.82-1.78 (m, 3H),1.48-1.42 (m, 1H), 1.31-1.20 (m, 3H). LC-MS m/z calcd for C₃₀H₃₆N₄O₃S,532.3; found 533.3 [M+H]⁺. HPLC purity 99.4%.

Biology Methods

TR-FRET Assay for LSD1 (Perkin Elmer)

LSD1 enzyme was produced in house. Tranylcypromine (TCP), LSD1 inhibitorwas procured from Selleckchem. LSD1 enzyme, TCP and Biotinylated peptidesubstrate were diluted in assay buffer just before use. 2× inhibitor (10μl, diluted in assay buffer) or Assay Buffer, and 5 nMenzyme were addedto a 96 well plate and incubated at room temperature for 30 min. 5 μL ofbiotinylated Histone H3K4me1 peptide (4×) was added to each well andincubated at room temperature (RT) for 1 hour. Stop Solution containing300 μM tranylcypromine in 1× LANCE Detection Buffer was added to thewells and incubated for 5 min at RT. Then, Detection mix containing 2 nMEu-Ab and 50 nM ULight-Streptavidin in 1× LANCE Detection Buffer wasprepared and added to the reaction mix. This mixture was incubated for 1hour at room temperature. Readings were taken with the Pherastar Readerin TR-FRET mode (excitation at 337 nm & emission at A-665 nm, B-620 nM).

Histone Deacetylase Assay (BPS Biosciences)

Histone deacetylase assay was done as per manufacturer's instructions.Briefly, assay buffer, 200 uM HDAC substrate (fluorogenic HDACacetylated peptide substrate for class I HDACs (HDACs 1, 2, and 3) andclass 2b HDACs (HDACs 6 and 10) and 1% BSA are taken as a master mix andaliquoted as 40 ul per well. Compounds (10×) were diluted in assaybuffer and were added to respective wells of a black 96 well plate.HDAC6 human recombinant enzyme was thawed on ice and 5 μl (7 ng/ul)enzyme was added per well. The plate was incubated at 37° C. for 1 hour.Developer solution was then added (50 μl per well) and incubated at roomtemperature for 10 minutes. Fluorescence was measured at an excitationwave length of 350-380 nm and emission wavelength of 440-480 nm.

As described above, compounds were tested for LSD1, HDAC1, HDAC2 andHDAC6 enzyme inhibitory activities.

Anticancer Activity: Alamar Blue Assay

Cells were seeded at 5000 cells/per well in 96-well tissue culture plateand incubated at 37° C./5% CO2. After 16-24 hours, fresh media was addedto the wells. Compounds were then (1% DMSO conc.) added to the cells at10 concentrations ranging from 10-0.0005 uM prepared in 3-fold serialdilutions. Cells were incubated for 68-72 h at 37° C./5% CO₂. AlamarBlue™ reagent was added and incubated for 1-3 hours at 37° C./5% CO2.Plates were read on fluorescence reader at 540 nm excitation, 590 nmemission wave lengths.

As described above, compounds were tested for anticancer activities indifferent tumor cell lines and GI₅₀ were determined.

Metabolic Stability

The microsomal suspension was prepared by adding liver microsomes to 100mM potassium phosphate buffer (pH7.4) to give a final proteinconcentration of 0.5 mg/mL. The stock solution of NCE (10 mM in DMSO)was added to the microsomes to provide a final concentration of 1 μM.Incubations were undertaken with NADPH (1 mM final concentration) for 0,5, 15 and 30 min at 37° C., after which reactions were quenched withacetonitrile (quench ratio 1:1). Samples were vortexed and centrifugedat 5,000 rpm for 10 min to remove proteins. Supernatant were analyzed onLC-MS/MS.

TABLE 1 Selected list compounds with Enzymatic, cellular activity andmetabolic stability Metabolic stability LSD1 HDAC6 MM1S HLM/MLM IC₅₀IC₅₀ EC₅₀ % remaining Compound uM uM uM in 30 min  1 0.083 ND ND 21/5  2 0.057 ND 0.023 41/19  3 0.020 ND 0.104 65/<5  4 0.684 ND ND ND  50.049 0.373 0.088 86/59  6 0.049 ND 0.034 44/<5  7 0.027 0.174 0.04870/<5  8 0.040 0.088 0.007 88/52  9 0.101 ND 0.004 65/50 10 0.221 ND0.009 81/55 11 0.019 ND 0.018 44/14 12 0.778 0.136 0.011 95/85 13 0.044ND 0.024 57/23 14 0.367 ND 0.008 88/82 15 0.095 0.134 0.012 ND 16 0.089ND 0.017 47/25 17 0.128 0.398 0.017 69/57 18 0.150 ND 0.003 41/28 190.309 ND 0.007 83/71 20 0.100 0.072 0.003 91/69 21 0.115 0.091 0.00986/51 22 6.4 0.171 0.044 60/38 23 0.778 0.136 0.011 95/85 24 1.160 ND0.009 71/74 25 0.840 ND 0.011 75/85 26 0.020 ND ND 30/13 27 0.016 >1.00 ND 75/51 28 0.023 0.264 ND 73/35 29 0.178 0.819 ND >95/90  30 0.1190.202 0.045 16/51 31 0.111 ND ND 39/18 32 0.070 ND 0.017 41/22 332.250 >1.00  ND ND 34 0.031 >1.00  0.094 90/79 35 0.034 0.199 1.429 ND36 0.011 0.235 ND 63/53 37 0.043 0.141 1.731 86/55 38 0.053 0.169 3.642 87/>95 39 0.034 0.732 2.969  87/>95 40 0.178 0.037 ND ND 41 0.319 0.074ND ND 42 0.015 0.49  0.19  ND 43 0.005 0.048 0.002 40/56 44 0.013 0.0650.045 71/55 45 0.465 ND 0.048 ND 46 0.026 0477 0.071 54/47 47 0.0060.051 0.033 54/66 48 0.029 0.184 0.025 85/<5 49 0.018 ND 0.062 48/34 500.029 0.212 0.035 86/80 51 0.006 0.038 0.002 74/91 52 0.004 0.012 0.00379/56 53 0.022 0.291 0.024 89/82 54 0.023 0.214 0.038 65/72 55 0.0220.130 0.189 40/36 56 0.002 0.019 0.001 87/75 57 0.021 0.059 0.006 92/7558 0.025 0.043 0.015 85/91 59 0.032 0.204 0.018 76/75 60 0.021 0.0460.024 73/72 61 0.012 0.121 0.049 77/66 62 0.043 0.066 0.007 77/66 630.031 1.315 0.191 86/69 64 0.059 0.058 0.011 82/77 65 0.038 0.383 0.026ND 66 0.019 0.100 0.021 79/85 67 0.484 0.272 0.070 ND 68 ND 0.104 ND ND71 1.1 0.028 ND 73/<5 72 0.730 0.018 0.343 67/<5 73 0.109 0.243 0.54052/53 74 0.028 0.112 0.253 47/27 75 0.286 0.365 0.246 ND 76 0.084 0.0220.042 ND 77 0.065 0.071 0.070 ND 78 0.103 0.183 0.060 72/32 79 0.0790.024 0.039 18/6  80 1.5 0.068 0.331 82/87 81 0.394 0.125 0.022 >95/>9582 0.094 0.035 0.619 77/72 83 0.090 0.179 0.153 69/82 84 0.057 0.0450.112 78/40  84A 0.107 0.022 0.026 78/41   84B 0.230 0.025 0.259 75/4585 0.062 0.575 >10     ND 86 0.018 0.554 0.676 71/58 87 0.025 1.0619.107 ND 88 ND 0.077 ND ND 89 0.020 0.720 0.311 ND 90 0.021 0.170 0.33980/93 91 0.332 0.138 0.468 85/79 92 0.273 0.115 1.4  95/91 93 0.0720.187 1.04  1.040 95 0.033 0.350 0.144 75/55 96 0.022 6.608 >10    93/89 97 0.033 >10 >10     ND 98 0.037 5.96  >10     ND 99 0.004 0.0510.027 63/76 100  0.023 ND 0.017 63/57 101  0.197 0.152 0.029 59/29 102 0.022 0.075 0.005 >99/>99 103  0.124 0.041 0.045 85/53  103A 0.667 0.0220.052 87/68  103B 0.154 0.036 0.015 76/73 104  0.206 0.032 0.269 80/77 104A 0.455 0.053 0.183 74/68  104B 1.002 0.045 0.374 74/70 105  0.1380.018 0.013 77/72 106  0.026 0.035 0.014 74/92 107  0.399 0.085 0.07883/67 108  0.134 0.195 0.584 >95/85  109  0.024 0.107 1.1  ND 110 0.026 >10 >10     88/95 111  0.022 2.98  3.065 95/91 112  0.022 0.5170.063 ND 113  0.026 >10 >10     78/76 114  0.051 0.068 0.044 83/56  114A0.063 0.038 0.014 67/62  114B 0.285 0.033 0.097 73/43 115  0.065 0.0530.010 75/45  115A 0.225 0.050 0.077 59/90 116  0.069 0.135 0.157 63/50117  0.046 0.074 0.460 80/82 118  0.037 0.058 0.021 77/76 119  0.0190.049 0.772 72/49 120  0.596 ND 0.361 27/16 121  0.006 ND 0.003 36/42122  0.006 ND 0.015 77/72 123  0.007 ND 0.009 82/72 124  0.019 ND 0.01473/68 125  0.021 ND — 34/49 126  0.032 ND 0.012 79/76 127  0.764 >100.126 17/19 128  0.128 >10 0.070 ND 129  ND >10 ND ND 132  0.005 >100.021 81/80 133  0.040 >10 ND 19/9  134  0.042 >10 0.174 10/10 135 0.145 >10 0.247 2/8 136  0.570 >10 0.174 4/3 137  0.139 >10 0.126 ND138  0.099 >10 0.065 ND 139  ND >10 ND ND 140  0.002 >10 0.002 85/83141  0.030 >10 0.194 88/75 142  0.012 >10 0.120 72/52 143  0.037 >100.102 37/50 144  0.041 >10 0.152 68/52 145  0.061 >10 0.123 ND 146 0.069 >10 0.106 ND 147  0.032 >10 0.029 48/<5 148  0.024 >10 0.040 46/34149  0.021 >10 >10     ND 150  0.016 >10 0.411 >95/>95 151  0.216 >100.345 30/18 152  0.306 >10 0.566 36/31 153  0.024 >10 0.571 ND 154 ND >10 ND ND 155  0.271 >10 0.042 46/34 156  0.186 >10 0.097 58/49 157 0.058 >10 0.167 53/63 158  0.171 >10 0.058 50/<5 160  0.043 >10 0.178 NDND: Not determined

TABLE 3 Anticancer profileration (EC₅₀ in μM)in different cell lines at144 hr- HEL- OCI- MV- CCRF- Compound 92.1.7 AML3 4-11 CEM MDAMB231 A3752 0.057 0.159 0.014 0.652 0.478 1.600 5 0.026 0.146 0.054 0.533 1.6002.300 8 0.042 0.046 0.048 0.119 0.193 0.698 10 0.089 0.089 0.026 0.1570.403 0.381 12 0.004 0.041 0.009 0.375 1.300 2.800 13 0.026 0.056 0.0100.378 1.100 1.300 43 0.001 0.115 0.002 0.493 0.747 1.030 47 0.005 0.1460.005 1.4  0.875 3.6  51 0.003 0.014 0.031 ND ND ND 52 0.005 0.022 0.0010.371 0.891 1.7  56 0.01 0.01 0.007 ND ND ND 71 6.05 0.732 0.990 ND NDND 72 4.8 0.573 0.978 ND ND ND 121 0.009 0.0007 0.004 ND ND NDIn Vivo PK Studies in Mice

All the animal experiments were approved by Institutional Animal EthicalCommittee (IAEC/JDC/2015/72). Male Balb/C mice (n=24) were procured fromVivo Biotech, Hyderabad, India. The animals were housed in JubilantBiosys animal house facility in a temperature (22±2° C.) and humidity(30-70%) controlled room (15 air changes/hour) with a 12:12 h light:darkcycles, had free access to rodent feed (Altromin Spezialfutter GmbH &Co. KG., Im Seelenkamp 20, D-32791, Lage, Germany) and water for oneweek before using for experimental purpose. Following ˜4 h fast (duringthe fasting period animals had free access to water) animals weredivided into two groups (n=12/group). Group I animals (27-29 g) receivedNCE orlaly at 10 mg/Kg (strength: 1.0 mg/mL; dose volume: 10 mL/Kg),whereas Group II animals (29-31 g) received NCE intravenously (strength:0.1 mg/mL; dose volume: 10 mL/Kg) at 2.0 mg/Kg dose. Post-dosing serialblood samples (100 μL, sparse sampling was done and at each time pointthree mice were used for blood sampling) were collected usingMicropipettes (Microcaps®; catalogue number: 1-000-0500) through tailvein into polypropylene tubes containing K₂.EDTA solution as ananti-coagulant at 0.25, 0.5, 1, 2, 4, 8, 10 and 24 (for oral study) and0.12, 0.25, 0.5, 1, 2, 4, 8 and 24 (for intravenous study). Plasma washarvested by centrifuging the blood using Biofuge (Hereaus, Germany) at1760 g for 5 min and stored frozen at −80±10° C. until analysis. Animalswere allowed to access feed 2 h post-dosing.

The criteria for acceptance of the analytical runs encompassed thefollowing: (i) 67% of the QC samples accuracy must be within 85-115% ofthe nominal concentration (ii) not less than 50% at each QCconcentration level must meet the acceptance criteria (US DHHS, FDA,CDER, 2001). Plasma concentration-time data of the compound was analyzedby non-compartmental method using Phoenix WinNonlin Version 6.3(Pharsight Corporation, Mountain View, Calif.).

TABLE 2 In vivo PK data Dose C₀- C_(Max)- AUC Cl V_(d) mg/kg ng/mL ng/mLng/mL/hr t_(1/2)-hr mL/min/Kg L/Kg Compound IV/PO IV IV/PO IV/PO IV/POIV IV F % 57 2/10 260 254/217 169/677 1.71/1.83 190 28 80  115A 2/10 452452/354 301/638 0.87/2.78 108 8 43 142  2/50 198 150/555  357/321712.6/6.7  88 25 36 61 10/50  5340 2758/771  1287/1920 2.80/1.48 125 3030Expression of Biomarkers Assessed by Western Blotting

Cell lysates were prepared in RIPA buffer (150 mM Tris-HCl, 150 mM NaCl,1% NP-40, 0.5% sodium deoxycholate, 0.1% SDS, 0.5 mM PMSF, 1× proteaseinhibitor cocktail) and 5-10 ug of protein was loaded for SDS-PAGE.Proteins were then transferred to a nitrocellulose membrane and thenprobed with respective antibodies. The bands of interest were visualizedby chemiluminescence. Antibodies used were H₃K4 mono, di and tri methylfrom Abcam, Acetyl alpha tubulin and acetyl histone (K9) from Cellsignaling technologies.

Expression of Biomarkers Assessed by qPCR

RNA was extracted from cells or tumor samples using the TRI reagent(manufacturer's protocol). Generally 1 μg RNA per sample is used with 10mM dNTPs and 50 μM Random primers (Thermo). The samples are kept at 65°C. for 5 minutes, then 1 min on ice and then the master mix (5× strandbuffer, 0.1M DTT, RNase out inhibitor, Superscript) is added to eachsample anth then the RT reaction is completed in a PCR machine (25° C.-5min, 50° C.-60 min, 70° C.-15 min). The 25-30 ng of cDNA thus preparedis used for the QPCR using respective primers for CD86, CD11b, GFi1B andβ actin. The SYBR Green qPCR plate is set up according to themanufacturer's protocols.

Xenograft Studies

Tumor CellImplantation and Randomization of Animals

Five million (5×10⁶) cells in 100 μl of serum free medium were mixedwith equal amount of matrigel and the entire the mixture was injectedsubcutaneously at the right flank region. The tumors were measured withVernier calipers periodically after first week of injection. When thetumor volume reached 120-150 mm³ (3-4 weeks after injection) the animalswere randomized into different groups so that their tumor volume isapproximately similar in all groups.

Determination of In Vivo Efficacy and Tumor Growth Inhibition

For PO dosing, the compounds were prepared in the formulation containing0.5% Methyl cellulose and 0.01% Tween 80. Animals were dosed withcompounds prepared in specific formulations at the required doses.Tumors size and body weights were measured twice or thrice a week.Tumors were harvested at the end of the study after euthanizing theanimals according to approved protocols. From the harvested tumor onepart was snap frozen and given for PK studies and the other half washomogenized and the lysates were tested for target inhibition usingwestern blotting. Before the tumor was harvested, blood (˜200 μL) wascollected by ocular bleeding for PK studies. Changes in tumor volume (Avolumes) for each treated (T) and control (C) group were calculated bysubtracting the mean tumor volume on the first day of treatment(starting day) from the mean tumor volume on the specified observationday. These values were used to calculate a percentage growth (% T/C)using the formula:% T/C=(ΔT/ΔC)×100where ΔT>0, or% T/C=(ΔT/ΔTi)×100Where ΔT<0 and Ti is the mean tumor volume at the start of theexperiment.

Percentage tumor growth inhibition was calculated as [100−% T/C].

We claim:
 1. A compound of Formula (I) or a stereoisomer, pharmaceutically acceptable salt, complex, hydrate, solvate, tautomer, polymorph, racemic mixture, and optically active form thereof, wherein the compound of Formula (I) is selected from a group consisting of: 1) (E)-3(4(((2(4cyclopropylphenyl)cyclopropyl)amino)methyl)phenyl)-N-hydroxyacrylamide TFA salt; 2) (E)-3-(4-{[2-(4-Fluoro-phenyl)-cyclopropylamino]-methyl}-phenyl)-N-hydroxy-acrylamide TFA salt; 3) (E)-3-(4-(((2-(4-((4-fluorobenzyl)oxy)phenyl)cyclopropyl)amino)methyl)phenyl)-N-hydroxyacrylamide TFA salt; 4) (E)-N-hydroxy-3-(4-(4-(((2-phenylcyclopropyl)amino)methyl)piperidin-1-yl)phenyl) acrylamide TFA salt; 5) (E)-3-(4-(((2-(4′-chloro-[1,1′-biphenyl]-4-yl)cyclopropyl)amino)methyl)phenyl)-N-hydroxyacrylamide TFA salt; 6) (E)-3-(4-(((2-(4-(3,5-dimethylisoxazol-4-yl)phenyl)cyclopropyl)amino)methyl)phenyl)-N-hydroxyacrylamide TFA salt; 7) (E)-N-hydroxy-3-(4-(((2-(4-(pyrimidin-5-yl)phenyl)cyclopropyl)amino)methyl)phenyl) acrylamide TFA salt; 8) 2-(4-(((2-(4-fluorophenyl)cyclopropyl)amino)methyl)piperidin-1-yl)-N-hydroxy pyrimidine-5-carboxamide TFA salt; 9) 2-[4-(2-Phenyl-cyclopropylamino)-piperidin-1-yl]-pyrimidine-5-carboxylicacid hydroxyamide TFA salt; 10) 2-{4-[2-(4-Fluoro-phenyl)-cyclopropylamino]-piperidin-1-yl}-pyrimidine-5-carboxylic acid hydroxyamide TFA salt; 11) 2-(4-(((2-(4-((4-fluorobenzyl)oxy)phenyl)cyclopropyl)amino)methyl)piperidin-1-yl)-N-hydroxypyrimidine-5-carboxamide TFA salt; 12) 2-(4-((2-(4-((4-fluorobenzyl)oxy)phenyl)cyclopropyl)amino)piperidin-1-yl)-N-hydroxypyrimidine-5-carboxamide TFA salt; 13) 2-(4-((2-(4′-chloro-[1,1′-biphenyl]-4-yl)cyclopropyl)amino)piperidin-1-yl)-N-hydroxypyrimidine-5-carboxamide TFA salt; 14) 2-(4-(((2-(4′-chloro-[1,1′-biphenyl]-4-yl)cyclopropyl)amino)methyl)piperidin-1-yl)-N-hydroxypyrimidine-5-carboxamide TFA salt; 15) 2-(4-(((2-(4′-fluoro-[1,1′-biphenyl]-4-yl)cyclopropyl)amino)methyl)piperidin-1-yl)-N-hydroxypyrimidine-5-carboxamide TFA salt; 16) 2-(4-(((2-(4-(3,5-dimethylisoxazol-4-yl)phenyl)cyclopropyl)amino)methyl)piperidin-1-yl)-N-hydroxypyrimidine-5-carboxamide TFA salt; 17) N-hydroxy-2-(4-(((2-(4-(pyrimidin-5-yl)phenyl)cyclopropyl)amino)methyl)piperidin-1-yl)pyrimidine-5-carboxamide TFA salt; 18) N-hydroxy-2-(4-(((2-(4-methoxyphenyl)cyclopropyl)amino)methyl)piperidin-1-yl)pyrimidine-5-carboxamide TFA salt; 19) N-hydroxy-2-(4-((2-(4-methoxyphenyl)cyclopropyl)amino)piperidin-1-yl)pyrimidine-5-carboxamide TFA salt; 20) 2-(4-((((1R,2S)-2-(4-fluorophenyl)cyclopropyl)amino)methyl)piperidin-1-yl)-N-hydroxypyrimidine-5-carboxamide TFA salt; 21) 2-(4-((((1S,2R)-2-(4-fluorophenyl)cyclopropyl)amino)methyl)piperidin-1-yl)-N-hydroxypyrimidine-5-carboxamide TFA salt; 22) 4-(4-(((2-(4-fluorophenyl)cyclopropyl)amino)methyl)piperidin-1-yl)-N-hydroxybenzamide TFA salt; 23) N-hydroxy-2-(2-(((2-phenylcyclopropyl)amino)methyl)-5,6-dihydroimidazo[1,2-a]pyrazin-7(8H)-yl)pyrimidine-5-carboxamide TFA salt; 24) N-hydroxy-2-(2-(((2-(4-methoxyphenyl)cyclopropyl)amino)methyl)-5,6-dihydroimidazo[1,2-a]pyrazin-7(8H)-yl)pyrimidine-5-carboxamide TFA salt; 25) 2-(2-(((2-(4-fluorophenyl)cyclopropyl)amino)methyl)-5,6-dihydroimidazo[1,2-a]pyrazin-7(8H)-yl)-N-hydroxypyrimidine-5-carboxamide TFA salt; 26) 3-(((2-(4-bromophenyl)cyclopropyl)amino)methyl)-N-hydroxybenzamide TFA salt; 27) N-hydroxy-3-(((2-phenylcyclopropyl)amino)methyl)benzamide TFA salt; 28) N-hydroxy-4-(((2-phenylcyclopropyl)amino)methyl)benzamide TFA salt; 29) N-hydroxy-6-((2-phenylcyclopropyl)amino)hexanamide TFA salt; 30) 4-(3-((2-(4-fluorophenyl)cyclopropyl)amino)propyl)-N-hydroxybenzamide TFA salt; 31) N-(6-Hydroxycarbamoyl-hexyl)-4-[(2-phenyl-cyclopropylamino)-methyl]-benzamide TFA salt; 32) 4-(((2-(4-fluorophenyl)cyclopropyl)amino)methyl)-N-(7-(hydroxyamino)-7-oxoheptyl)benzamide TFA salt; 33) 4-(2-Phenyl-cyclopropylamino)-cyclohexanecarboxylic acid hydroxyamide TFA salt; 34) (1S,4R)-N-hydroxy-4-((1S)-1-((2phenylcyclopropyl)amino)ethyl)cyclohexanecarboxamide TFA salt; 35) N-hydroxy-4-((4-(((2-(4-(1-methyl-6-oxo-1,6-dihydropyridin-3-yl)phenyl)cyclopropyl)amino)methyl)piperidin-1-yl)methyl)benzamide TFA salt; 36) N-Hydroxy-4-{4-[(2-phenyl-cyclopropylamino)-methyl]-piperidin-1-ylmethyl}-benzamide TFA salt; 37) 4-((4-(((2-(4-(3,5-dimethylisoxazol-4-yl)phenyl)cyclopropyl)amino)methyl)piperidin-1-yl) methyl)-N-hydroxybenzamide TFA salt; 38) N-hydroxy-4-((4-(((2-(4-(pyrimidin-5-yl)phenyl)cyclopropyl)amino)methyl)piperidin-1-yl)methyl)benzamide TFA salt; 39) 6-((4-(((2-(4-(3,5-dimethylisoxazol-4-yl)phenyl)cyclopropyl)amino)methyl)piperidin-1-yl)methyl)-N-hydroxynicotinamide TFA salt; 40) N-hydroxy-4-((4-(((2-phenylcyclopropyl)amino)methyl)-1H-pyrazol-1-yl)methyl) benzamide TFA salt; 41) N-hydroxy-4-((4-(((2-phenylcyclopropyl)amino)methyl)-1H-1,2,3-triazol-1-yl) methyl)benzamide TFA salt; 42) N-hydroxy-4-(2-(4-(((2-phenylcyclopropyl)amino)methyl)piperidin-1-yl)ethyl)benzamide TFA salt; 43) N-hydroxy-4-(3-(4-(((2-phenylcyclopropyl)amino)methyl)piperidin-1-yl)propyl)benzamide TFA salt; 44) N-hydroxy-4-(3-(4-((2-phenylcyclopropyl)amino)piperidin-1-yl)propyl)benzamide TFA salt; 45) N-hydroxy-4-(3-(4-((methyl (2-phenylcyclopropyl) amino) methyl) piperidin-1-yl) propyl)benzamide TFA salt; 46) N-hydroxy-4-(3-(6-((2-phenylcyclopropyl)amino)-2-azaspiro[3.3]heptan-2-1)propyl) benzamide TFA salt; 47) 4-[3-(4-{[2-(4-Fluoro-phenyl)-cyclopropylamino]-methyl}-piperidin-1-yl)-propyl]-N-hydroxy-benzamide TFA salt; 48) 4-(3-(3-(((2-(4-fluorophenyl)cyclopropyl)amino)methyl)azetidin-1-yl)propyl)-N-hydroxy benzamide TFA salt; 49) 4-(3-(4-(((2-(3-fluorophenyl)cyclopropyl)amino)methyl)piperidin-1-yl)propyl)-N-hydroxy benzamide TFA salt; 50) 4-(3-(4-(((2-(3,4-difluorophenyl)cyclopropyl)amino)methyl)piperidin-1-yl)propyl)-N-hydroxybenzamide TFA salt; 51) N-hydroxy-4-(3-(4-(((2-(4-methoxyphenyl)cyclopropyl)amino)methyl)piperidin-1-yl)propyl)benzamide TFA salt; 52) N-hydroxy-4-(3-(4-(((2-(4-(morpholine-4-carbonyl)phenyl)cyclopropyl)amino)methyl)piperidin-1-yl)propyl)benzamide TFA salt; 53) N-hydroxy-4-(3-(4-(((2-(4-(morpholine-4-carbonyl)phenyl)cyclopropyl)amino)methyl)piperidin-1-yl)propyl)benzamide TFA salt; 54) N-hydroxy-4-(3-(4-(((2-(4-(piperidine-1-carbonyl)phenyl)cyclopropyl)amino)methyl)piperidin-1-yl)propyl)benzamide TFA salt; 55) N-(2-(dimethylamino)ethyl)-4-(2-(((1-(3-(4-(hydroxycarbamoyl)phenyl)propyl)piperidin-4-yl)methyl)amino)cyclopropyl)benzamide TFA salt; 56) 4-(3-(4-(((2-(4′-chloro-[1,1′-biphenyl]-4-yl)cyclopropyl)amino)methyl)piperidin-1-yl)propyl)-N-hydroxybenzamide TFA salt; 57) 4-(3-(4-(((2-(4′-fluoro-[1,1′-biphenyl]-4-yl)cyclopropyl)amino)methyl)piperidin-1-yl)propyl)-N-hydroxybenzamide TFA salt; 58) 4-(3-(3-(((2-(4′-fluoro-[1,1′-biphenyl]-4-yl)cyclopropyl)amino)methyl)azetidin-1-yl) propyl)-N-hydroxybenzamide; 59) 4-(3-(4-(((2-(4′-cyano-[1,1′-biphenyl]-4-yl)cyclopropyl)amino)methyl)piperidin-1-yl)propyl)-N-hydroxybenzamideTFA salt; 60) N-hydroxy-4-(3-(4-(((2-(4-(1-methyl-2-oxo-1,2-dihydropyridin-4-yl)phenyl)cyclopropyl) amino)methyl)piperidin-1-yl)propyl)benzamide TFA salt; 61) N-hydroxy-4-(3-(4-(((2-(4-(pyrimidin-5-yl)phenyl)cyclopropyl)amino)methyl)piperidin-1-yl)propyl)benzamide TFA salt; 62) N-hydroxy-4-(3-(4-(((2-(4-(1-methyl-1H-pyrazol-4-yl)phenyl)cyclopropyl)amino) methyl)piperidin-1-yl) propyl) benzamide TFA salt; 63) N-hydroxy-4-(3-(3-(((2-(4-(1-methyl-1H-pyrazol-4-yl)phenyl)cyclopropyl)amino) methyl) azetidin-1-yl)propyl)benzamide; 64) 4-(3-(4-(((2-(4-(3,5-dimethylisoxazol-4-yl)phenyl)cyclopropyl)amino)methyl)piperidin-1-yl)propyl)-N-hydroxybenzamide TFA salt; 65) 3-(3-(3-(((2-(4-(3,5-dimethylisoxazol-4-yl)phenyl)cyclopropyl)amino)methyl)azetidin-1-yl)propyl)-N-hydroxybenzamide TFA salt; 66) N-hydroxy-4-(3-(4-(((2-(4-(6-(trifluoromethyl)pyridin-3-yl)phenyl)cyclopropyl)amino)methyl)piperidin-1-yl)propyl)benzamide TFA salt; 67) N-hydroxy-4-(3-(4-(((2-(1-isopropyl-1H-pyrazol-4-yl)cyclopropyl)amino)methyl)piperidin-1-yl)propyl)benzamide TFA salt; 68) N-hydroxy-4-(3-(4-(((2-(1-phenyl-1H-pyrazol-4-yl)cyclopropyl)amino)methyl)piperidin-1-yl)propyl)benzamide TFA salt; 69) N-hydroxy-4-(3-(4-(((2-(2-methylthiazol-5-yl)cyclopropyl)amino)methyl)piperidin-1-yl)propyl)benzamide TFA salt; 70) N-hydroxy-4-(3-(4-(((2-(pyridin-3-yl)cyclopropyl)amino)methyl)piperidin-1-yl)propyl) benzamide TFA salt; 71) N-hydroxy-4-(3-(2-(((2-(4-methoxyphenyl)cyclopropyl)amino)methyl)-5,6-dihydroimidazo[1,2-a]pyrazin-7(8H)-yl)propyl)benzamide TFA salt; 72) 4-(3-(2-(((2-(4-fluorophenyl)cyclopropyl)amino)methyl)-5,6-dihydroimidazo[1,2-a]pyrazin-7(8H)-yl)propyl)-N-hydroxybenzamide TFA salt; 73) 4-(3-(4-(((2-(3,4-difluorophenyl)cyclopropyl)amino)methyl)-1H-imidazol-1-yl) propyl)-N-hydroxybenzamide TFA salt; 74) N-hydroxy-4-(3-(4-(((2-phenylcyclopropyl)amino)methyl)-1H-imidazol-1-yl)propyl) benzamide TFA salt; 75) N-hydroxy-4-(3-(4-(((2-phenylcyclopropyl)amino)methyl)-1H-imidazol-1-yl)propyl) benzamide; 76) N-hydroxy-4-(3-(4-(((2-phenylcyclopropyl)amino)methyl)-1H-pyrazol-1-yl)propyl) benzamide TFA salt; 77) N-hydroxy-4-(3-(4-(((2-phenylcyclopropyl)amino)methyl)-1H-1,2,3-triazol-1-yl)propyl)benzamide TFA salt; 78) 4-(3-(6-(((2-(4-fluorophenyl)cyclopropyl)amino)methyl)-3,4-dihydroisoquinolin-2-(1H)-yl)propyl)-N-hydroxybenzamide TFA salt; 79) 4-((7-(((2-(4-fluorophenyl)cyclopropyl)amino)methyl)-3,4-dihydroisoquinolin-2(1H)-yl)methyl)-N-hydroxybenzamide TFA salt; 80) 4-((2-(((2-(4-fluorophenyl)cyclopropyl)amino)methyl)-5,6-dihydroimidazo[1,2-a]pyrazin-7 (8H)-yl)methyl)-N-hydroxybenzamide TFA salt; 81) N-hydroxy-4-(3-(4(((2-(1,3,3,-trimethyl-2-oxoindoline-5-yl)cyclopropyl)amino)methyl) piperidine-1-yl)propyl)benzamide TFA salt; 82) N-hydroxy-4-(3-oxo-3-(4-(((2-phenylcyclopropyl)amino)methyl)piperidin-1-yl)propyl)benzamide TFA salt; 83) N-hydroxy-4-(3-oxo-3-(4-((2-phenylcyclopropyl)amino)piperidin-1-yl)propyl)benzamide TFA salt; 84) N-hydroxy-4-(2-oxo-2-(4-(((2-phenylcyclopropyl)amino)methyl)piperidin-1-yl)ethyl) benzamide TFA salt; 84A. N-hydroxy-4-(2-oxo-2-(4-((((1R,2S)-2-phenylcyclopropyl)amino)methyl)piperidin-1-yl) ethyl)benzamide; 84B. N-hydroxy-4-(2-oxo-2-(4-((((1S,2R)-2-phenylcyclopropyl)amino)methyl)piperidin-1-yl) ethyl)benzamide; 85) N-hydroxy-4-((4-(((2-phenylcyclopropyl)amino)methyl)piperidin-1-yl)sulfonyl) benzamide TFA salt; 86) N-hydroxy-4-((N-(2-(4-(((2-phenylcyclopropyl)amino)methyl)piperidin-1-yl)ethyl) sulfamoyl)methyl)benzamide TFA salt; 87) 4-(N-(2-(4-(((2-(4-fluorophenyl)cyclopropyl)amino)methyl)piperidin-1-yl)ethyl) sulfamoyl)-N-hydroxybenzamide; 88) N-hydroxy-4-(2-((4-(((2-phenylcyclopropyl)amino)methyl)piperidin-1-yl)sulfonyl)ethyl) benzamide TFA salt; 89) N-hydroxy-N4-(2-(4-(((2-phenylcyclopropyl)amino)methyl)piperidin-1-yl)ethyl) terephthalamide TFA salt; 90) N1-(2-(4-(((2-(3,4-difluorophenyl)cyclopropyl)amino)methyl)piperidin-1-yl)ethyl)-N4-hydroxyterephthalamide TFA salt; 91) N-hydroxy-4-((4-(2-((2-phenylcyclopropyl)amino)acetyl)piperazin-1-yl)methyl)benzamide TFA salt; 92) N-hydroxy-4-(3-oxo-3-(4-(2-((2-phenylcyclopropyl)amino)acetyl)piperazin-1-yl)propyl)benzamide TFA salt; 93) N-hydroxy-4-(3-(1-(2-((2-phenylcyclopropyl)amino)acetyl)piperidin-4-yl)propyl)benzamide TFA salt; 94) N-hydroxy-4-(3-(2-oxo-4-(((2-phenylcyclopropyl)amino)methyl)piperidin-1-yl) propyl)benzamide TFA salt; 95) N-hydroxy-4-(2-((2-phenylcyclopropyl)amino)ethoxy)benzamide TFA salt; 96) 6-(2-(4-(((2-(4-fluorophenyl)cyclopropyl)amino)methyl)piperidin-1-yl)ethoxy)-N-hydroxynicotinamide TFA salt; 97) N-hydroxy-6-(2-(4-(((2-phenylcyclopropyl)amino)methyl)piperidin-1-yl)ethoxy)nicotinamide TFA salt; 98) 6-(2-(4-(((2-(4′-fluoro-[1,1′-biphenyl]-4-yl)cyclopropyl)amino)methyl)piperidin-1-yl) ethoxy)-N-hydroxynicotinamide TFA salt; 99) N-hydroxy-4-(2-(4-(((2-phenylcyclopropyl)amino)methyl)piperidin-1-yl)ethoxy)benzamide TFA salt; 100) N-hydroxy-4-(3-(4-(((2-phenylcyclopropyl)amino)methyl)piperidin-1-yl)propoxy)benzamide TFA salt; 101) N-hydroxy-4-(3-((2-phenylcyclopropyl)amino)propoxy)benzamide TFA salt; 102) 2-((2-(4-(((2-(4-fluorophenyl)cyclopropyl)amino)methyl)piperidin-1-yl)ethyl)amino)-N-hydroxypyrimidine-5-carboxamide TFA salt; 103) 5-(2-((2-(4-fluorophenyl)cyclopropyl)amino)acetyl)-N-hydroxy-4,5,6,7-tetrahydro thieno[3,2-c]pyridine-2-carboxamide TFA salt; 103A) 5-(2-(((1R,2S)-2-(4-fluorophenyl)cyclopropyl)amino)acetyl)-N-hydroxy-4,5,6,7-tetrahydrothieno[3,2-c]pyridine-2-carboxamide; 103B) 5-(2-(((1S,2R)-2-(4-fluorophenyl)cyclopropyl)amino)acetyl)-N-hydroxy-4,5,6,7-tetrahydrothieno[3,2-c]pyridine-2-carboxamide; 104) 2-(2-((2-(4-fluorophenyl)cyclopropyl)amino)acetyl)-N-hydroxy-1,2,3,4-tetrahydro isoquinoline-7-carboxamide TFA salt; 104A) 2-(2-(((1S,2R)-2-(4-fluorophenyl)cyclopropyl)amino)acetyl)-N-hydroxy-1,2,3,4-tetrahydroisoquinoline-7-carboxamide; 104B) 2-(2-(((1R,2S)-2-(4-fluorophenyl)cyclopropyl)amino)acetyl)-N-hydroxy-1,2,3,4-tetrahydroisoquinoline-7-carboxamide; 105) 5-(4-((2-(4-fluorophenyl)cyclopropyl)amino)butanoyl)-N-hydroxy-4,5,6,7-tetrahydro thieno[3,2-c]pyridine-2-carboxamide TFA salt; 106) 5-(4-(4-(((2-(4-fluorophenyl)cyclopropyl)amino)methyl)piperidin-1-yl)butanoyl)-N-hydroxy-4,5,6,7-tetrahydrothieno[3,2-c]pyridine-2-carboxamide TFA salt; 107) 2-(4-((2-(4-fluorophenyl)cyclopropyl)amino)butanoyl)-N-hydroxy-1,2,3,4-tetrahydro isoquinoline-7-carboxamide TFA salt; 108) 2-(4-((2-(4-fluorophenyl)cyclopropyl)amino)butanoyl)-N-hydroxyisoindoline-5-carboxamide TFA salt; 109) N-hydroxy-2-(4-(4-(((2-phenylcyclopropyl)amino)methyl)piperidin-1-yl)butanoyl) isoindoline-5-carboxamide TFA salt; 110) N-hydroxy-2-(3-(4-(((2-phenylcyclopropyl)amino)methyl)piperidin-1-yl)propyl) thiazole-4-carboxamide TFA salt; 111) 2-(3-(4-(((2-(4′-fluoro-[1,1′-biphenyl]-4-yl)cyclopropyl)amino)methyl)piperidin-1-yl)propyl)-N-hydroxythiazole-4-carboxamide; 112) N-hydroxy-2-(3-(4-(((2-phenylcyclopropyl)amino)methyl)piperidin-1-yl)propyl) thiazole-5-carboxamide TFA salt; 113) N-hydroxy-2-(3-(4-(((2-phenylcyclopropyl)amino)methyl)piperidin-1-yl)propyl) oxazole-4-carboxamide; 114) (E)-N-hydroxy-4-(3-oxo-3-(4-(((2-phenylcyclopropyl)amino)methyl)piperidin-1-yl) prop-1-en-1-yl)benzamide TFA salt; 114A) N-hydroxy-4-((E)-3-oxo-3-(4-((((1R,2S)-2-phenylcyclopropyl)amino)methyl) piperidin-1-yl)prop-1-en-1-yl)benzamide TFA salt; 114B) N-hydroxy-4-((E)-3-oxo-3-(4-((((1S,2R)-2-phenylcyclopropyl)amino)methyl) piperidin-1-yl)prop-1-en-1-yl)benzamide TFA salt; 115) 4-((E)-3-(4-((((1S,2R)-2-(4-fluorophenyl)cyclopropyl)amino)methyl) piperidin-1-yl)-3-oxoprop-1-en-1-yl)-N-hydroxybenzamide TFA salt; 115A) 4-((E)-3-(4-((((1S,2R)-2-(4-fluorophenyl)cyclopropyl)amino)methyl) piperidin-1-yl)-3-oxoprop-1-en-1-yl)-N-hydroxybenzamide TFA salt; 116) (E)-4-(3-(4-(((2-(4-(3,5-dimethylisoxazol-4-yl)phenyl)cyclopropyl)amino)methyl) piperidin-1-yl)-3-oxoprop-1-en-1-yl)-N-hydroxybenzamide TFA salt; 117) (E)-N-hydroxy-4-(3-oxo-3-(4-(((2-(4-(pyrimidin-5-yl)phenyl)cyclopropyl)amino) methyl)piperidin-1-yl)prop-1-en-1-yl)benzamide TFA salt; 118) (E)-4-(3-(3-(((2-(4-fluorophenyl)cyclopropyl)amino)methyl)azetidin-1-yl)-3-oxoprop-1-en-1-yl)-N-hydroxybenzamide TFA salt; 119) (E)-N-hydroxy-4-(3-(3-(((2-(4-(1-methyl-1H-pyrazol-4-yl)phenyl)cyclopropyl)amino)methyl)azetidin-1-yl)-3-oxoprop-1-en-1-yl)benzamide TFA salt; 120) (E)-N-(2-aminophenyl)-3-(4-(((2-(4-fluorophenyl)cyclopropyl)amino)methyl)phenyl)acrylamide TFA salt; 121) N-(2-aminophenyl)-4-(3-(4-(((2-phenylcyclopropyl)amino)methyl)piperidin-1-yl)propyl)benzamide TFA salt; 122) N-(2-aminophenyl)-4-(3-(4-(((2-(4-fluorophenyl)cyclopropyl)amino)methyl)piperidin-1-yl)propyl)benzamide TFA salt; 123) N-(2-aminophenyl)-4-(3-(4-(((2-(4-methoxyphenyl)cyclopropyl)amino)methyl)piperidin-1-yl)propyl)benzamide TFA salt; 124) N-(2-aminophenyl)-4-(3-(4-(((2-(3,4-difluorophenyl)cyclopropyl)amino)methyl) piperidin-1-yl)propyl)benzamide TFA salt; 125) N-(2-aminophenyl)-4-(3-(4-(((2-(4-(piperidine-1-carbonyl)phenyl)cyclopropyl)amino)methyl)piperidin-1-yl)propyl)benzamide TFA salt; 126) N-(2-aminophenyl)-4-(3-(3-(((2-(4-fluorophenyl)cyclopropyl)amino)methyl)azetidin-1-yl) propyl)benzamide TFA salt; 127) N-(2-aminophenyl)-4-(3-(6-((2-phenylcyclopropyl)amino)-2-azaspiro[3.3]heptan-2-yl)propyl)benzamide TFA salt; 128) N-(2-aminophenyl)-4-(3-(4-(((2-(1-isopropyl-1H-pyrazol-4-yl)cyclopropyl)amino)methyl)piperidin-1-yl)propyl)benzamide TFA salt; 129) N-(2-aminophenyl)-4-(3-(4-(((2-(1-phenyl-1H-pyrazol-4-yl)cyclopropyl)amino)methyl)piperidin-1-yl)propyl)benzamide TFA salt; 130) N-(2-aminophenyl)-4-(3-(4-(((2-(2-methylthiazol-5-yl)cyclopropyl)amino)methyl) piperidin-1-yl)propyl)benzamide TFA salt; 131) N-(2-aminophenyl)-4-(3-(4-(((2-(pyridin-3-yl)cyclopropyl)amino)methyl)piperidin-1-yl)propyl)benzamide TFA salt; 132) N-(2-amino-5-fluorophenyl)-4-(3-(4-(((2-(4-fluorophenyl)cyclopropyl)amino)methyl)piperidin-1-yl)propyl)benzamide TFA salt; 133) N-(2-aminophenyl)-4-(3-oxo-3-(4-((2-phenylcyclopropyl)amino)piperidin-1-yl)propyl)benzamide TFA salt; 134) N-(2-aminophenyl)-4-(3-oxo-3-(4-(((2-phenylcyclopropyl)amino)methyl)piperidin-1-yl)propyl)benzamide TFA salt; 135) N-(2-aminophenyl)-4-(3-(4-(((2-(3,4-difluorophenyl)cyclopropyl)amino)methyl)-1H-imidazol-1-yl)propyl)benzamide TFA salt; 136) N-(2-aminophenyl)-4-(3-(4-(((2-phenylcyclopropyl)amino)methyl)-1H-imidazol-1-yl)propyl)benzamide; 137) N-(2-aminophenyl)-4-(3-(4-(((2-phenylcyclopropyl)amino)methyl)-1H-1,2,3-triazol-1-yl)propyl)benzamide TFA salt; 138) N-(2-aminophenyl)-4-(3-(4-(((2-phenylcyclopropyl)amino)methyl)-1H-pyrazol-1-yl)propyl)benzamideTFA salt; 139) N-(2-aminophenyl)-4-(2-(4-(((2-phenylcyclopropyl)amino)methyl)piperidin-1-yl) ethyl)benzamide TFA salt; 140) N-(2-aminophenyl)-4-((4-((((1R,2S)-2-phenylcyclopropyl)amino)methyl)piperidin-1-yl) methyl)benzamide TFA salt; 141) N-(2-aminophenyl)-4-((4-(((2-(4-(1-methyl-6-oxo-1,6-dihydropyridin-3-yl)phenyl) cyclopropyl)amino)methyl)piperidin-1-yl)methyl)benzamide TFA salt; 142) N-(2-aminophenyl)-4-((4-(((2-(4-(1-methyl-1H-pyrazol-4-yl)phenyl)cyclopropyl)amino)methyl)piperidin-1-yl)methyl)benzamide TFA salt; 143) N-(2-aminophenyl)-4-((4-(((2-(4-(3,5-dimethylisoxazol-4-yl)phenyl)cyclopropyl)amino) methyl)piperidin-1-yl)methyl)benzamide TFA salt; 144) N-(2-aminophenyl)-4-((4-(((2-(4-(pyrimidin-5-yl)phenyl)cyclopropyl)amino)methyl)piperidin-1-yl)methyl)benzamide TFA salt; 145) N-(2-aminophenyl)-4-((4-(((2-phenylcyclopropyl)amino)methyl)-1H-pyrazol-1-yl)methyl)benzamide TFA salt; 146) N-(2-aminophenyl)-4-((4-(((2-phenylcyclopropyl)amino)methyl)-1H-1,2,3-triazol-1-yl)methyl)benzamide TFA salt; 147) N-(2-aminophenyl)-4-(2-(4-(((2-(4-fluorophenyl)cyclopropyl)amino)methyl)piperidin-1-yl)-2-oxoethyl)benzamide TFA salt; 148) N-(2-aminophenyl)-4-(2-((2-(4-fluorophenyl)cyclopropyl)amino)ethoxy)benzamide TFA salt; 149) N-(2-aminophenyl)-6-(2-(4-(((2-(4-fluorophenyl)cyclopropyl)amino)methyl)piperidin-1-yl)ethoxy)nicotinamide TFA salt; 150) N-(-2-aminophenyl)-2-((2-4(((2-(4-flurophenyl)cyclopropyl)amino)methyl)piperdine-1-yl)ethyl)amino)pyrimidine-5-carboxamide TFA salt; 151) N-(2-aminophenyl)-5-((2-(4-fluorophenyl)cyclopropyl)glycyl)-4,5,6,7-tetrahydrothieno[3,2-c]pyridine-2-carboxamide TFA salt; 152) N-(2-aminophenyl)-2-(2-((2-(4-fluorophenyl)cyclopropyl)amino)acetyl)-1,2,3,4-tetrahydroisoquinoline-7-carboxamide TFA salt; 153) N-(2-aminophenyl)-2-(3-(4-(((2-phenylcyclopropyl)amino)methyl)piperidin-1-yl)propyl)oxazole-4-carboxamide TFA salt; 154) N-(2-aminophenyl)-2-(3-(4-(((2-phenylcyclopropyl)amino)methyl)piperidin-1-yl)propyl)thiazole-5-carboxamide TFA salt; 155) N-(2-aminophenyl)-4-((2-((2-(4-fluorophenyl)cyclopropyl)amino)acetamido) methyl)benzamide TFA salt; 156) (E)-N-(2-aminophenyl)-4-(3-(4-(((2-(4-fluorophenyl)cyclopropyl)amino)methyl)piperidin-1-yl)-3-oxoprop-1-en-1-yl)benzamide TFA salt; 157) (E)-N-(2-aminophenyl)-4-(3-(3-(((2-(4-fluorophenyl)cyclopropyl)amino)methyl)azetidin-1-yl)-3-oxoprop-1-en-1-yl)benzamide TFA salt; 158) N-(4-((2-aminophenyl)carbamoyl)benzyl)-4-(((2-(4-fluorophenyl)cyclopropyl)amino)methyl)piperidine-1-carboxamide TFA salt; 159) N-(2-aminophenyl)-4-(3-(2-oxo-4-(((2-phenylcyclopropyl)amino)methyl)piperidin-1-yl)propyl)benzamide; 160) N-(2-aminophenyl)-4-((4-(((2-phenylcyclopropyl)amino)methyl)piperidin-1-yl)sulfonyl) benzamide TFA salt; 161) N-(2-aminophenyl)-4-(((4-(((2-phenylcyclopropyl)amino)methyl)piperidin-1-yl)sulfonyl)methyl)benzamide TFA salt; 162) N-(2-aminophenyl)-4-(2-((4-(((2-phenylcyclopropyl)amino)methyl)piperidin-1-yl)sulfonyl)ethyl)benzamide TFA salt.
 2. A process of preparation of a compound of Formula (I) as claimed in claim 1 or a tautomer, polymorph, stereoisomer, solvate, or pharmaceutically acceptable salt thereof, the process comprising the steps of Scheme 1

wherein: Ar is selected from the group consisting of substituted or unsubstituted C₅₋₆aryl, C₁₋₆heteroaryl, and C₂₋₁₀heterocyclyl with heteroatoms selected from N, O, S; W represents a bond or CR₄R₅, wherein R₄ and R₅ are independently selected from the group consisting of hydrogen, and substituted or unsubstituted C₁₋₈alkyl; Y is selected from the group consisting of substituted or unsubstituted C₁₋₈alkyl, C₅₋₆aryl, C₁₋₆heteroaryl, C₂₋₁₀heterocyclyl, C₃₋₈cycloalkyl, and —CO—C₂₋₁₀heterocyclyl; wherein C₁₋₈alkyl, C₅₋₆aryl, C₁₋₆heteroaryl, C₂₋₁₀heterocyclyl, and C₃₋₈cycloalkyl, is optionally substituted with one or more of the groups selected from hydrogen, C₁₋₆ alkyl, and oxo (═O); Z represents a bond or is selected from the group consisting of C₁₋₈alkyl, C₂₋₈alkenyl, C₇₋₁₂-alkylaryl, C₇₋₁₅-arylalkenyl, C₂₋₁₂-alkylheteroaryl, —CO—C₇₋₁₂alkylaryl, —CO—C₇₋₁₂alkenylaryl, —CONR₆-C₁₋₈ alkyl, CONR₆—C₅₋₆aryl-, C₅₋₆aryl, C₁₋₆heteroaryl, C₂₋₁₀ heterocyclyl, —CO—C₂₋₁₀ heterocyclyl, —NR₆CO—C₅₋₆aryl-, —NR₆—C₅₋₆aryl, NR₆—C₁₋₆heteroaryl, —C₁₋₈alkyl-O—C₅₋₆aryl, —O—C₅₋₆aryl, O—C₁₋₆heteroaryl, —CONR₆-C₇₋₁₂alkylaryl, —SO₂—C₅₋₆aryl, —SO₂—C₇₋₁₂alkylaryl, —NR₆SO₂—C₇₋₁₂alkyl aryl, C₁₋₈alkyl-CONR₆—C₅₋₆aryl, and OCONR₆—C₅₋₆aryl; R₆ is selected from the group consisting of hydrogen, and C₁₋₈ alkyl; R₁ is selected from the group consisting of hydrogen, halogen, oxo (═O), C₁₋₈alkyl, C₁₋₈haloalkyl, C₁₋₈alkoxy, C₃₋₈cycloalkyl, C₅₋₆aryl, C₂₋₁₀heterocyclyl, C₁₋₆heteroaryl, —C(O)R_(b), —C(O)NR_(a)R_(b), and —OR_(a), wherein R_(a) and R_(b) is independently selected from the group consisting of hydrogen, C₁₋₈alkyl, C₅₋₆aryl, C₇₋₁₅arylalkyl and C₂₋₁₀heterocyclyl with heteroatoms selected from N, O, S; and wherein C₁₋₈alkyl, C₅₋₆aryl, C₁₋₆heteroaryl, C₂₋₁₀heterocyclyl, and C₃₋₈cycloalkyl, is optionally substituted with one or more of the groups selected from hydrogen, C₁₋₆ alkyl, oxo(═O), halogen, and cyano; R₃ is selected from the group consisting of hydrogen, and substituted or unsubstituted C₁₋₈alkyl; R₂ is selected from the group consisting of —OR₇ and aniline, wherein aniline is optionally substituted with one or more halogen and R₇ is hydrogen; Step 1 comprises reacting compound 1 with at least one reducing agent or at least one alkylating agent in the presence of inorganic or organic base to obtain a compound 2; Step 2 comprises hydrolyzing the compound 2 with an inorganic base to obtain an acid; followed by coupling the acid with at least one activating agent selected from 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride or 1-propylphosphonic anhydride in the presence of 1-hydroxybenzotriazole or triethylamine and at least one substituted amine (NH₂R₂) to yield the compound of Formula (I).
 3. A pharmaceutical composition comprising a compound of Formula (I) or a pharmaceutically acceptable salt thereof as claimed in claim 1 together with a pharmaceutically acceptable carrier, optionally in combination with one or more other pharmaceutical compositions.
 4. The pharmaceutical composition as claimed in claim 3, wherein the composition is in the form selected from the group consisting of a tablet, capsule, powder, syrup, solution, aerosol and suspension.
 5. A method of inhibiting LSD1 in a cell, comprising treating said cell with an effective amount of a compound as claimed in claim 1, or a pharmaceutically acceptable salt thereof.
 6. A method of treating a condition mediated by LSD1 comprising administering to a subject suffering from a condition mediated by LSD1, a therapeutically effective amount of the compound as claimed in claim 1 or a pharmaceutically acceptable salt thereof, or the pharmaceutical composition according to claim 3, wherein the condition is breast cancer, prostate cancer, lung cancer, colon cancer, rectal cancer, brain tumor, non-small cell lung cancer, small cell lung cancer, liver cancer, urinary & bladder cancer, or thyroid cancer.
 7. A method of treating a condition mediated by LSD1 comprising administering to a subject suffering from a condition mediated by LSD1, a therapeutically effective amount of the compound as claimed in claim 1 or a pharmaceutically acceptable salt thereof, or the pharmaceutical composition according to claim 3, wherein the condition is acute myelogenous leukemia (AML). 